Cancer.Net Podcast (American Society of Clinical Oncology (ASCO))

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Every year, the ASCO Annual Meeting brings together attendees from around the globe to learn about the latest research in the treatment and care of people with cancer. This year, attendees from 138 countries worldwide gathered virtually for the ASCO20 Virtual Scientific Program, held Friday, May 29 through Sunday, May 31.

In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, “What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?” In this final episode of 2020, editors discuss new research in the fields of central nervous system tumors and lymphoma.

First, Dr. Glenn Lesser will discuss new research on a form of non-Hodgkin lymphoma that begins in the central nervous system, and research into a possible treatment for breast cancer that has spread to the brain. Dr. Lesser is the Louise McMichael Miracle Professor and Associate Chief in the section on Hematology and Oncology in the Department of Internal Medicine at Wake Forest University, with joint appointments in the Departments of Anesthesiology, Neurosurgery, and Public Health Sciences. He is also the Cancer.Net Associate Editor for Central Nervous System Tumors.

View Dr. Lesser’s disclosures at Cancer.Net.

Dr. Lesser: Hello. My name is Glenn Lesser, and I'm a professor of medical oncology and director of medical neuro-oncology at the Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina. I'm also the editor of the brain tumor section for ASCO's Cancer.Net. And today, I would like to briefly discuss what I think are 2 of the most clinically relevant research studies on brain tumors that were presented at this year's ASCO's Virtual Scientific Program. I should say right up front I have no disclosures or relationships that are relevant to the particular studies I'll be discussing today.

Unlike the progress we've seen in the treatment of many cancers over the past few years, patients with brain tumors and the physicians who care for them have not seen the same rapid advance in effective treatment strategies. Cancer that begins in the brain, so-called primary brain tumors, and the more common situation of cancer that spreads to the brain after originating elsewhere in the body, so-called metastatic or secondary brain tumors, still have relatively few effective treatment options available. However, I believe that the 2 abstracts we'll discuss today may impact the way that we treat certain primary and metastatic brain tumors in the future.

The first study I'd like to talk about was presented by Dr. Omuro on behalf of a group of international colleagues that described a randomized study of standard chemotherapy with or without low dose whole brain radiation in patients with a brain tumor known as a primary central nervous system lymphoma, which I may also talk about as a PCNSL for abbreviation. Non-Hodgkin's lymphoma is a relatively common cancer that involves the blood and lymph nodes throughout the body. Primary central nervous system lymphoma is the term used when patients develop a non-Hodgkin's lymphoma that's confined to the central nervous system which is really made up of the brain, the spinal cord, the spinal nerves, and the spinal fluid. This turns out to be a pretty rare diagnosis with only about 1,500 new cases of this cancer occurring in this country each year. This type of lymphoma is important, though, because it's very treatable in most patients, and a significant percentage of our patients can be cured with appropriate therapy. Because the disease is so rare, we really don't have the results of large clinical trials to help us determine the best treatment approach for patients with primary central nervous system lymphoma. And as a result, there are a variety of controversies over how to initially treat patients who develop this lymphoma, so-called induction therapy, as well as what type of treatment to give once the disease has been made to go away, or so-called consolidation therapy. In the past, radiation therapy to the whole brain was used to treat patients with PCNSL. And most of these patients who were treated with radiation-containing regimens had their tumors respond, although the cancer frequently returned within a year or 2. This approach has really fallen out of favor over the last few decades because of the very high incidence of neurotoxicity or brain damage from the radiation that was seen in surviving patients.

Unfortunately, a significant number of those patients who were treated with high doses of whole-brain radiation therapy developed a progressive irreversible dementia over the years following the radiation treatments, and a particularly high incidence of this toxicity was seen in patients who are over the age of 50. With current multi-agent chemotherapy regimens, a high percentage of treated patients are having their lymphomas go away. Unfortunately, a significant number of patients still have their disease come back within months or years of this treatment. And so strategies to consolidate or lock in that initial good result with treatment are being evaluated. These strategies may involve high doses of different types of chemotherapies, consideration of bone marrow or stem cell transplant, and even long-term maintenance treatment with oral chemotherapies. More recently, low doses of whole-brain radiation therapy have been explored as a way to try to prevent these lymphomas from coming back with a thought that the low doses of radiation might have minimal long-term brain toxicity as compared to the high doses of radiation given in the past.

So this study that was presented at ASCO involved about 91 patients with primary central nervous system lymphoma. Half of them received the low-dose whole-brain radiation therapy after their tumors were treated with several months of multi-agent chemotherapy, while the other half did not get the radiation. After a follow-up period of 4 to 5 years, the results of this treatment were that the patients who received the low-dose radiation in addition to chemotherapy lived longer and had a significantly higher rate of their tumor going away and staying away at least at the 2-year follow-up tie point. Now, data is not yet available on the neurocognitive outcomes in both groups of patients. That is how well their brains were functioning with tasks like memory, calculations, and personality. The improved results seen in this group of patients who got radiation suggests that this approach may be one effective way of helping to consolidate the treatment of primary central nervous system lymphoma after the induction chemotherapy.

These results, however, can only really be fully interpreted and applied once we have more long-term information on whether the patients treated in this fashion suffer from the high rate of neurotoxicity and dementia that was seen in prior studies using the higher doses of radiation. With further follow-up, this study should provide us with some definitive information on whether the strategy of adding low-dose radiation following standard induction chemotherapy is a good one for patients with primary central nervous system lymphoma.

The second study I'd like to talk about was presented by Dr. Nancy Lin, again on behalf of an international group of colleagues, and described the results of a trial adding a new drug called tucatinib to a standard chemotherapy regimen of trastuzumab and capecitabine in women with HER2-positive breast cancer involving the brain. Now, many common cancers have a tendency to spread to the brain if they recur after initial treatment. This metastatic or secondary involvement of the brain occurs in over 200,000 patients a year in the U.S., and new treatments for brain metastases are desperately needed. Women with advanced breast cancer are particularly susceptible to developing brain metastases, particularly if they have the subtype of breast cancer known as HER2-positive disease. In HER2-positive disease is defined that way because of the presence of the HER2 protein on the surface of breast cancer cells. Although a number of effective treatments have been developed for patients with HER2-positive breast cancer involving the body, including some common drugs like trastuzumab and pertuzumab, these agents have not been particularly effective in either treating breast cancer that has spread to the brain or preventing the breast cancer from spreading to the brain in the first place.

One of the main reasons why these chemotherapy drugs have not been effective in treating breast cancer metastases in the brain is that unlike the other organs in our bodies, the blood vessels of the brain are formed in such a way that they carefully restrict what substances in the blood are able to leave the blood and spread into the brain. Normal blood vessels in our body are somewhat leaky. And fluids, proteins, drugs can leak out of those vessels into the tissue with some freedom. The blood vessels of the brain, however, are lined by cells that tightly joined together to create a blood-brain barrier that is not leaky, and that barrier protects the brain from compounds that are circulating in our bloodstream which could adversely affect brain function if they were able to get into the brain in any concentration. Because of this barrier, most of our standard chemotherapy and anticancer drugs simply cannot cross the barrier to reach the cancer cells within the brain. In part, because of this, patients whose cancer had spread to the brain have typically been excluded from most of the clinical trials evaluating new drugs and treatments for breast cancer. The study reported by Lin at ASCO tested the ability of a new HER2-targeted drug, tucatinib, which because of its chemical structure has good penetration across this blood-brain barrier. Earlier smaller studies had suggested that this drug did indeed get into the brain at concentrations that could effectively treat breast cancer involving the brain. In this study, almost 300 patients with metastatic breast cancer involving the brain were treated with a standard chemotherapy regimen with or without the tucatinib. Serial brain scans were obtained in order to measure the response of the brain metastases to the treatment. These were typically MRI scans of the brain.

The study results showed that the use of tucatinib in patients with breast cancer involving the brain reduce the risk of the growth of their brain disease by about two-thirds and improve their overall survival by at least 6 months. These results have recently been published in a more complete form in the Journal of Clinical Oncology. And these results really strongly support the use of tucatinib in combination with the standard chemotherapy regimen of trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer involving the brain.

Although neither of the new approaches I've just described cure the majority of patients treated with either the primary CNS lymphoma or brain metastases from breast cancer, both describe new approaches that really potentially move us further along the road to having more effective treatments for patients with brain tumors. These studies are also outstanding examples of why well-done clinical trials that carefully test and evaluate the beneficial effects as well as the toxicities of new cancer treatments are critical to our goal of finding new therapies to treat our patients with cancer. Thanks very much.

ASCO: Thank you, Dr. Lesser.

Next, Dr. Michael Williams will discuss several studies that looked at new ways to treat different types of lymphoma. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center. He is also the Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine. He is also the Cancer.Net Associate Editor for Lymphoma.

View Dr. William’s disclosures at Cancer.Net.

Dr. Williams: Hello. This is Dr. Michael Williams. I'm a professor of medicine at the University of Virginia hospital in Charlottesville, Virginia, where I'm chief of the hematology oncology division and the physician lead for cancer services here at UVA. I have a few disclosures, clinical trial grant support from Janssen and Pharmacyclics to the University of Virginia. I've received honoraria for medical education conferences from Xian Janssen, and I have been a consultant for Kite Pharmaceuticals in the past. So what we're going to talk about today are some of the highlights in lymphoma that were presented at the recent virtual meeting of the American Society of Clinical Oncology focused on lymphoma. So the field continues to move forward very rapidly. It's really a dynamic time for advances in treatment of lymphoma and related disorders. The exciting thing is that patients in the not-too-distant past may have had limited options, especially in the setting of recurrent lymphoma. We now have new approaches that are really quite interesting, quite effective, and I think are going to change the way we practice for these particular diseases.

So the first of these I'm going to talk about is for classical Hodgkin lymphoma, also called Hodgkin's disease. So the good news is here, that the vast majority of people with Hodgkin lymphoma are cured by their frontline therapy but not all do achieve a remission, or if they do, they may relapse a year or 2 or sometimes later after their initial therapy. And these patients, historically, have not had as good of a long-term outcome as those who remained in their initial remission. So investigators from an international team of lymphoma experts conducted the KEYNOTE-204 study that compared an immune checkpoint inhibitor - it's a form of immunotherapy called pembrolizumab - versus a standard agent brentuximab vedotin, which is a drug antibody conjugate that delivers a chemotherapy agent directly to the Hodgkin tumor cells. So these were patients who had either not responded to their initial treatment, in other words were considered to be primary refractory, or had relapsed later. Many of them relapsed within 12 months, which is, again, a worrisome timing for relapse in that those patients may be more chemotherapy resistant to traditional treatments.

So in this study, it was a 1-to-1 comparison of about 300 patients. And the study found that those who received the checkpoint inhibitor pembrolizumab had a better response in terms of their remission rate and a more long-lasting response than those patients treated with brentuximab vedotin. At 12 months, about 54% of patients remained in remission as opposed to about a third of patients on brentuximab. Although, there were some continued relapses over the next year, there were some patients who achieved more durable response. So it was a very encouraging finding. The side effects were as would be expected. There were some autoimmune problems with the immunotherapy checkpoint inhibitor and peripheral neuropathy in those who got brentuximab. So these investigators concluded that for patients with this form of relapsed and chemotherapy-resistant Hodgkin's lymphoma, that pembrolizumab should be considered the preferred treatment option and a new standard of care for these patients.

Now, the second trial that we'll talk about relates to a specific form of non-Hodgkin lymphoma called lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. This is a lymphoma where an abnormal immunoglobulin, a high molecular weight IgM, is produced. That can cause problems of hyper viscosity and headaches, vision changes, shortness of breath, in addition to some lymphoma-related symptoms. And what they did is compared 2 targeted agents for people who needed treatment, whether they were relapsed or had not had prior treatment at all for their Waldenstrom's. And the drugs that they chose were Bruton tyrosine kinase, or BTK, inhibitors. These are a very active class of drugs in B-cell lymphomas including Waldenstrom's. And the first of these that became available several years ago and was FDA approved is ibrutinib, and a second agent more recently approved is zanubrutinib. The latter being a bit more targeted to the molecule that we're trying to inhibit in the tumor cells. And it's similar in many ways to a third drug that's available called acalabrutinib.

But in this study, they're comparing ibrutinib with zanubrutinib. And what they found is that, in about 200 patients, that both drugs were very effective in achieving a response. Slightly higher response rates for zanubrutinib, but really no significant difference in the progression-free and overall survival for these patients. So both drugs were very active and very reasonable for treating patients. There were fewer side effects, however, with zanubrutinib, in particular toxicities such as the development of atrial fibrillation and diarrhea or bruising and bleeding, which happened in a small percentage of patients on ibrutinib. So those side effects seemed to be less with the more targeted drug zanubrutinib. So they appeared to be similar in efficacy but perhaps a better safety and toxicity profile with zanubrutinib. Now, ibrutinib is approved in the United States for relapsed Waldenstrom macroglobulinemia. Zanubrutinib is approved for mantle cell lymphoma, so not for Waldenstrom.

So the final entity that I want to discuss is really using a treatment that many of you no doubt have read about. There's been a lot in the news about the use of CAR T-cell, or chimeric antigen receptor T-cell therapy. So this is a form of cellular therapy. And by that, I mean that in patients who have relapsed aggressive lymphoma, usually diffuse large B-cell, a patient who has relapsed disease has T-cells. Those are part of their immune cellular defenses. And those T-cells are removed and they're genetically reprogrammed and then expanded and reinfused to patients. So they're reprogrammed so that the immune effects are targeted against the patient's lymphoma cells. So this is an approved therapy in aggressive relapsed large B-cell lymphoma. But at this meeting, investigators from a number of centers in the United States reported the interim results of a study using a CAR T-cell called axicabtagene ciloleucel, or Axi-cel, for patients with indolent or low grade lymphoma that, nonetheless, is recurring, needs treatment, and has been resistant to at least 2 or more prior therapies.

So I'm going to focus in this study on the results with follicular lymphoma. They did also study a small number of patients with another type of indolent low-grade lymphoma called marginal zone. But looking at the follicular lymphoma patients, they were heavily pre-treated. Most of the patients had had 3 or more prior therapies. Most of them were refractory or, in other words, resistant to the current and the most recent chemotherapy they had received. And about a quarter of the patients had had a prior stem cell transplantation for relapsed disease but had now relapsed even after that therapy. And what they found in the first 80 follicular lymphoma patients they studied is that 95% of them responded and 81% achieved a complete remission. The duration of response was really quite good. So with a follow-up of a little over a year, about two-thirds of patients were still in remission. Whether these patients may be cured of their follicular lymphoma or may experience a later relapse is going to require more follow up, but very promising early results for this treatment of patients with otherwise resistant follicular lymphoma.

There are significant side effects with this type of therapy, including something called cytokine release syndrome, which is like an intense inflammatory reaction. Fortunately, the severe forms of this occurred in a minority of patients, under 10%. There can also be neurologic events that can range from tremor or confusion, and rarely even patients becoming unresponsive. Fortunately, most everyone recovers from this. And in this trial, the more severe forms of these neurologic events occurred in about 15% of patients. So a very promising early set of data for another group of lymphoma patients, in addition to those with large cell lymphoma. So if you are in a situation of highly resistant and progressing follicular lymphoma, including follicular lymphoma that may have transformed from the lower grade into a higher grade large cell lymphoma, then considering a CAR T-cell therapy or a clinical trial of other novel approaches is certainly worth considering.

And I'll finish by just saying that it's a fast-moving field. There's a lot of benefit if you have a newly diagnosed or a relapsed lymphoma to talk with your oncologist and consider whether a second opinion may be in order and what clinical trials might be relevant for your situation because, nowadays, we often find that taking part in such a trial provides access to some of these very promising new agents and allows us to move the field forward and bring these newer treatments online so that they can benefit as many patients as possible. So a very exciting time in the field of lymphoma, lots of important new data presented at ASCO, and I'll look forward to updating you on future advances in another podcast.

ASCO: Thank you, Dr. Williams. Learn more about the research presented at the ASCO20 Virtual Scientific Program at www.cancer.net/blog, and subscribe to Cancer.Net podcasts on Apple Podcasts or Google Play to catch up on the other episodes in the Research Round Up series.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

ASCO President Dr. Monica Bertagnolli has chosen “Caring for every patient. Learning from every patient,” as her presidential theme. Putting actions to words, from 2018 to 2019, she is hosting a series of ASCO Presidential Community Town Halls with local groups across the United States to hear from patients, providers, and the general public about real-world barriers to quality cancer care and to talk about ways to provide the best care to every person diagnosed with cancer.

In today’s podcast, Dr. Colin Weekes and the Reverend Joel Guillemette discuss the recent town hall event they hosted at the Sudbury United Methodist Church in Sudbury, Massachusetts on September 10. They discuss the most important issues in cancer care faced by members of this community, and ways that these kind of community events can support people with cancer and address these issues.

Dr. Weekes is director of Medical Oncology Research for Pancreatic Cancer at Massachusetts General Hospital. Pastor Joel is the Senior Pastor at the Sudbury United Methodist Church.

ASCO would like to thank Dr. Weekes and Pastor Joel for discussing this topic.

Dr. Weekes: Hi, Pastor Joel. I am Colin Weekes, one of the medical oncologists at Mass General Hospital and a member of ASCO. Would you take this moment to introduce yourself, sir?

Pastor Joel Guillemette: I'm Joel Guillemette. I'm the United Methodist pastor in Sudbury, Massachusetts.

Dr. Weekes: And I'd like to thank you for agreeing to participate in this podcast and really thank you for allowing us, ASCO, to come to your church and do what we've called the Cancer 101 Town Hall meeting at your church. And I was wondering if you could just take a little bit of time to talk about what you thought the impact of that event was, and why you thought that was important for us to come and talk to your parishioners?

Pastor Joel Guillemette: Well, the way I remember how the meeting began, Colin, you had a session in Dorchester, Massachusetts, with the Greenwood Memorial UMC, our sister church. And they were very excited about what happened in their conversation with you and recommended to us that we do something like that here in Sudbury, which is what? 20, 25 miles away. So our Health Ministries team had worked on an invitation to you and to the community. We were gratified by the number of people who came from our own congregation. We didn't see anybody that we would have identified as somebody from the wider community, but it was a good opportunity to talk, I think, about what the expectations of a group of people in an affluent suburb of Boston might be thinking when they hear a cancer diagnosis and begin to process all of that with you, and Dr. Bertagnolli who was also quite helpful in terms of representing some of the dos and don'ts of oncological practice here in the Boston area.

Dr. Weekes: From our perspective, I thought it was really exciting to be able to engage the community and start to talk about cancer from the perspective of the patient, which is something that I don't often get to do, given that most of the time my interaction with patients is in a clinic space. We're talking about sort of treatment and how do we proceed with the issue at hand. So for me, it was really interesting to just sort of hear the perspective of the patients and things that maybe we could do a little bit better in terms of communication, and trying to help patients organize their thoughts around how to manage such a problem.

Pastor Joel Guillemette: What did you hear?

Dr. Weekes: One of the conversations that I thought was really interesting was this idea of sort of how to not take away hope by the language that we use and the issues that we do or don't talk about. So I take care of patients with pancreas cancer, so unfortunately most of those patients will succumb to their disease. And so one of the questions that I posed to the audience was, "Should we be discussing that particular issue at the beginning of our interaction with patients with the context of trying to help the patients form goals around their care and sort of what they want to accomplish with their care and help to make decisions?" And I think we got sort of a variety of feedback in terms of how to approach that question.

And so some of the parishioners said, "Look, our doctor's always been very, very positive. We've never really discussed issues of death and dying. My particular loved one has lived a long time. I don't think we need to be discussing that." The converse was, another patient in the room said, "Now, look, I need to know what the situation is so I can plan. And once I know what the situation is, then I'm going to plan appropriately. And so in my case, I very much want to know what the situation was that I was facing." Now, I'm curious, as a minister who helps support these patients and their families, I think that's just a very challenging position to be in. And so I'm just curious. How do you approach that situation, and what are the things that you focus on as you're trying to help patients go through this process?

Pastor Joel Guillemette: Well, there's a lot in that question [laughter]. I think it is challenging. On the one hand, there's a teaching role in ministry where I think the expectation in the congregation is that clergy are going to teach us in the course of our being together what our faith has in terms of resources for the trials and challenges of life. And so you want to believe that what you've been teaching in the pulpit, in the classroom, will actually show up when cancer is the diagnosis. On the other hand, it sure didn't feel to me during our town meeting that that was happening. I mean, you spoke about never take away hope. I would have liked to have heard something like, "Well, I always have hope, one way or another, because I'm a Christian." And hope is a given because God is in my life, and whatever happens to me I'm being held up by God.

So that's not so much what I heard, and so there was this part of me as an ordained minister, as somebody who walks with people through cancer care, that was disappointed. On the other hand, I know from my training in chaplaincy-type skills that it's not my job to impose my solution on the patient, in terms of what he or she needs to believe to be well in the situation. It's my job to help them find whatever resources they can find in their own personal belief system, whatever that might be. And for most American Christians, that's going to be an amalgam of many things, but then to walk with them and to continue asking them, "Well, what resources do you find in what you believe, and is that working for you?"

Dr. Weekes: Right. Right. I guess one question I have for you is, how do you manage this issue of mortality? Because at the end of the day, cancer, the big C word, ultimately we're dealing with mortality. And how do you approach helping your parishioners, the family members, the patients sort of walk through that process? And maybe sometimes, even if there's a difference of opinion about how to get there, how do you manage that?

Pastor Joel Guillemette: Well, I want to know-- because it's really client-centered care, from my point of view, my responsibility is to ask the person for whom I'm caring, "What do you need, and how can I help you get that?" I was having a conversation some time ago with a cancer patient who's just very anxious about her diagnosis, and we began to talk about some ways to get at that anxiety. And the thing that seemed to have the most promise for her was that maybe she could learn some meditation kinds of techniques, some very deliberate breathing, what Christians called breath prayer. And to find in that some ways to relax even just with the treatments, the chemotherapy, and just going and being—and I'm not even sure what the word that I'm looking for is. Infused?

Dr. Weekes: Yeah, chemotherapy infused. Yeah, yeah.

Pastor Joel Guillemette: Infused. Just being infused was a terribly frightening experience for her. So I taught her breath prayer. We practiced. And next time I see her I want to know how that worked, and we'll go from there. But others are farther along. They know that death is coming. We might want to talk about, "What are your spiritual values that you want to pass on to your family members in a kind of a will? And do you want to write that down? Do you want to create a document, a letter to your family saying, 'Here's what I have believed and what my life has been about, and I'm bequeathing that to you'?" So those are powerful moments that can happen when people choose to be mindful about what's happening to them and rather than to be in denial about what's happening.

Dr. Weekes: Do you ever find a situation where maybe the patient understands that things are not going the way that we would all hope and that maybe they will succumb to the disease soon?

Pastor Joel Guillemette: Yeah.

Dr. Weekes: And the family is maybe not quite there. Yeah. And so to some degree sometimes that can potentially cause some difference of opinion within a family. How do you help patients and their families manage that situation?

Pastor Joel Guillemette: Yeah. That's a powerful question because it happens more than one might think. I think cancer patients understand that their family wants them to fight, then expects that they will put all of the strength they have into a fight against cancer, which most patients who are facing terrible cancer recognize it's a fight they're not going to win. So they're being set up for a battle that is almost always going to disappoint somebody. And so sometimes with a clergy, caregiver, or chaplain, I think cancer patients find that that's the one person with whom they can be totally honest.

Dr. Weekes: Mm-hmm.

Pastor Joel Guillemette: That people can say to me whatever they need to say. I think it's really valuable. I've been in hospital rooms when the family is there, and there was this big talk about how we're going to fight this, we're all in it together, and then finally the family members say, "Well, the pastor is here. I'm going to leave you alone." And out the door they go. They go home. They go to the cafeteria in the hospital, whatever. And then the patient says to me, "Now I can tell you how tired I am of fighting. I want to put my strength into something else. I only have a little time. And I would rather be working on this part of the relationship with my family rather than on a fight that I can't win."

Dr. Weekes: Wow. That's a powerful revelation.

Pastor Joel Guillemette: Yeah, yeah, yeah. Yeah. I mean, I was surprised at the town meeting, Colin, that there was so much unanimity around just wanting to deny that death is even in the room. For me that was sort of a revelation of how powerful Gnosticism is in America. If I can believe it, I can get it.

Dr. Weekes: Well, I mean, it's also the power to want to live which I think is—

Pastor Joel Guillemette: Do you think that's what it is? Yeah. I don't know.

Dr. Weekes: I mean, I think it could be a little bit of both, but I do find that it's very interesting particularly now that we've got our new therapies, some of which are targeted on different molecular abnormalities. Now with also our ability to sort of harness the immune system to treat cancer. I think it's a challenging conversation because there are times when, as a practitioner, you would say, "Okay, well, this patient is moving towards the end." And then you find that they have this molecular abnormality. You might be able to treat them for that, and then things turn around significantly. So I think the good thing about our new cancer care treatments is that we really can impact a wider breadth of patients in a substantial way. I think from the perspective of things that we're talking about now, it becomes a little bit challenging in terms of how to guide patients along that path. Now, sometimes we'll know the information about the molecular characterization much earlier in the disease process because we're doing that more commonly sort of upfront than how in the past maybe you would have done it sort of towards the end of the cancer treatment paradigm. So I think it is kind of challenging to sort of balance, I would say, this perspective of potentially the cancer winning and the patient succumbing to that cancer versus helping the patient realize that maybe there are other highly effective treatments if you have the right sort of molecular characterization, and trying to balance how to keep those two things [crosstalk].

Pastor Joel Guillemette: I agree that people I talk to as a pastor put a lot of hope in therapies that are not yet known. "Will there be a discovery in time for me?" That's something I hear a lot. But I'm thinking largely of the cancers for which we don't yet have that therapy, and that the reality is that death is coming. And yet still we want to have a positive outlook because there's a sense that—I feel like people are saying, "If you can envision it, you will have it." You know?

Dr. Weekes: Mm-hmm.

Pastor Joel Guillemette: And I also wonder—there's a segue in this observation that I think is important to include in our conversation today. I also wonder if that's part of living in a community where visioning has very often gotten what we want. I mean, this is an affluent community, people here, and not that people inherited their money by and large. Folks in this congregation, more than half of them, were the first generation in their family to go to college, so they've done well. And a lot of what the American dream is all about has been theirs from hard work and perseverance and a positive outlook. Right?

Dr. Weekes: Absolutely. Absolutely.

Pastor Joel Guillemette: And yet one of the things we talked about at the Cancer 101 workshop that you led is the disparity in cancer care zip code by zip code, and how in a community like ours the possibility for a more positive outcome is better than in communities where economic challenge is more prevalent. And yet our congregation has always said that we want to be on the side of God's justice and a more equal sharing of benefits and blessings. But that's not happening, and I wonder if it happens or not. I wonder how much our grasping after those privileges in communities like mine might keep that away from other communities.

Dr. Weekes: That's a very good question. I think this is a huge societal issue, right?

Pastor Joel Guillemette: Yeah.

Dr. Weekes: And problem in terms of how do we best manage our resources particularly when the resources are not infinite?

Pastor Joel Guillemette: Yeah. You didn't use the F word there, finite.

Dr. Weekes: Yes.

Pastor Joel Guillemette: The resources are finite. And so I think, to put my clergy hat back on, to be looking at the ultimate diagnosis, the diagnosis that none of us wants to hear, is an opportunity to put our focus back on the only one whose resources are infinite, you know?

Dr. Weekes: Yeah.

Pastor Joel Guillemette: And if we're people of faith, to find there the connection that will see us through to whatever grandeur of life might hold beyond this life.

Dr. Weekes: Well, I think that I've definitely been informed and sort of thinking about this from a different perspective. And I think some of the issues that you brought up are extreme food for thought for the community at large. And as a person who takes care of these patients, I think what struck me the most is the conversation where you sort of talk about the difference of opinion in terms of the patient's mortality, the patient relative to their family because I think, as a clinical investigator, I'm always thinking about sort of how can we treat patients better, how can we get more new treatments, and so forth. And sometimes thinking about the fact that patients may make their decisions based upon what they perceive others want for them versus what they truly want. I think the question for me is now how do I navigate that and help patients? How to even recognize that and then help patients through that process?

Pastor Joel Guillemette: And I have to say, hearing you talk about the cutting-edge treatments for cancer that, I mean, your face just lit up when you began to describe some of the new possibilities that science is making possible. That was encouraging for me. I need to hear that the door isn't always closed, and that maybe there are possibilities for looking beyond that we haven't had before. As we do that, I want to be able to share those possibilities in all of the zip codes of our community and not just some.

Dr. Weekes: Yeah. Well, Pastor Joel, I'd like to thank you for your time. This has been an amazing conversation.

Pastor Joel Guillemette: Thank you, Dr. Weekes.

Dr. Weekes: And I look forward to continuing the conversation over time.

Pastor Joel Guillemette: Thank you.

Dr. Weekes: All right.

ASCO: Thank you, Dr. Weekes and Pastor Joel. Learn more about past and upcoming ASCO Presidential Community Town Halls at www.cancer.net/townhall. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

Cancer.Net is supported by ASCO’s Conquer Cancer Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

In this podcast, Dr. Paul Celano discusses what patients should know when taking medication for cancer treatment, including tips for safely storing the medication, special considerations for oral chemotherapy and opioids, as well as resources to help dispose of unneeded or expired medications.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today’s podcast, 4 Cancer.Net Specialty Editors discuss new research in prostate, bladder, kidney, and testicular cancers presented at the 2021 Genitourinary Cancers Symposium, and 2021 ASCO Annual Meeting.

This episode has been adapted from the recording of a live Cancer.Net webinar, held June 16th, 2021, and led by Dr. Neeraj Agarwal, Dr. Tian Zhang, Dr. Petros Grivas, and Dr. Timothy Gilligan.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah.

Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center.

Dr. Zhang is an associate professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Institute.

Full disclosures for Dr. Agarwal, Dr. Grivas, Dr. Zhang, and Dr. Gilligan are available at Cancer.Net.

Greg Guthrie: So today, let's introduce our participants. First we have Dr. Neeraj Agarwal of Huntsman Cancer Institute and University of Utah and the Cancer.Net Specialty Editor for Prostate Cancer. Next we have Dr. Petros Grivas from Fred Hutchinson Cancer Research Center and University of Washington. He is the Specialty Editor for Cancer.Net for Bladder Cancer.

Next we have Dr. Tian Zhang of Duke Cancer Institute. And she's our Cancer.Net Specialty Editor for Kidney Cancer. And last, we have Dr. Timothy Gilligan. He is with the Cleveland Clinical Taussig Cancer Institute and the Specialty Editor for Testicular Cancer. So to start off, we'll have Dr. Agarwal talking about prostate cancer.

Dr. Agarwal: Thank you, Greg. It's such a privilege and honor to be here discussing these studies. So I would like to start with the first study, which was led by Dr. Stephen Freedland, a urologist at the Cedars-Sinai Medical Center in Los Angeles and was co-authored by me, Dr. Dan George, and many others. And here in this study, we present the utilization of therapies, which are associated and known to be associated with very significant, in fact, I would say dramatic improvement in overall survival, as shown by multiple randomized control trials over the period of the last 5 to 6 years. Just to take a step back for the audience, until 2014, standard treatment for metastatic castration-sensitive prostate cancer or newly diagnosed metastatic castration-sensitive prostate cancer used to be androgen deprivation therapy. And combining androgen deprivation therapy with those medications which were approved in the castration-resistant metastatic prostate cancer setting. So basically, using those drugs upfront led to dramatic improvement in overall survival with 33% to 35% reduction in risk of death across those clinical trials. So we actually wanted to look at the real-world utilization, so look at the real-world users of these medications in these patients who are being diagnosed with -- newly diagnosed metastatic prostate cancer in the United States. We also wanted to see how patients who belong to minority populations or racial minority populations, how they are being treated with these medications, which are backed by level 1 evidence. So this was a retrospective analysis of a Medicare database, more than 35,000 patients were included from 2009 to 2018. And we can see here a very representative patient population, predominantly white patients, 11.8% were African American, and 5% were Hispanic.

And here are the results. From 2010 to 2014, the use of standard androgen deprivation therapy with bicalutamide, was used in 97% of patients. We did not have trials reporting by that. Let's go to 2015 to 2016. Docetaxel was already approved in this setting now, and we can see some patients received docetaxel, but a small minority of patients received docetaxel. And then let's move to 2018, which is 4 or 5 years after docetaxel data had been presented by Dr. Sweeney in the ASCO plenary session. And abirateron was approved in 2017, and we are still seeing even like almost 2 years after -- we are still seeing the vast majority of patients being treated with standard androgen deprivation therapy or standard deprivation therapy with bicalutamide. So 62% plus 19%, we are talking about almost 80% of patients still not being treated with standard of care treatment, which is androgen deprivation therapy plus docetaxel, or androgen deprivation therapy plus abiraterone at this point of time, and now we have 2 more drugs available, which include enzalutamide and apalutamide in this study.

Another interesting thing was if you look at the patients who belong to minority populations, so let's look at African American patients compared to Caucasian patients. The use of intensified therapy was numerically lower. So in Caucasian patients, we are seeing higher use of intensified, as we call them, intensified therapy, or therapies which are considered standard of care, compared to African American men. So overall, the use was lower across the board, but if you look at African American men, the usage was even lower. So this is definitely concerning. I call it alarming, underutilization of life-prolonging therapy in patients who are being diagnosed with newly -- or new diagnosis of metastatic prostate cancer, and we definitely can improve this. We can definitely offer better care to our patients. It is not acceptable in my view to have 30% or less patients receiving standard of care therapies. So with that, I'll go to the next study.

 Greg Guthrie: Great, thanks. And this study is, “Health-related quality of life and patient-reported outcomes at final analysis of the TITAN study of apalutamide versus placebo in patients with metastatic castration-sensitive prostate cancer receiving androgen-deprivation therapy.” And you were the presenting author of this, Dr. Agarwal?

Dr. Agarwal: Yes, Greg, thank you for giving the opportunity to present this study. And this is basically the continuation of the previous trial. I will not delve into in-depth analysis of these data. I just wanted to show that quality of life is not being impacted adversely by using intensified androgen deprivation therapy, so if you are using these drugs, which improves survival in a very significant fashion, and they are not being used in our patients, as we just saw in the previous study, what could be the reason? Is it the concerns about quality of life or adverse impact on quality of life? If that is the concern, this study, I think, helps refute those concerns. And in this study, which was a large study known as the TITAN trial, which led to approval of apalutamide for patients with hormone-sensitive or castration-sensitive metastatic prostate cancer and showed improved survival and radiographic progression-free and overall survival. We looked at quality of life data as reported by these patients, and these quality-of-life data were assessed by very standardized, validated scales known as FACT-P, or Functional Assessment of Cancer Therapy Prostate scale, or Brief Pain Inventory tool. And there are many other tools. So I will show you the results. And we can see here consistently there was no difference in quality of life as reported by the patients, or I would say any adverse impact on quality of life for these patients in any of these questions. As they were taking these questionnaires. So whether it was physical wellness, emotional wellness, functional well-being, social, or family, we go in and look at fatigue and there was no adverse impact on quality of life. At least from this perspective, we should not be concerned about using these drugs up front in our patients who have newly diagnosed metastatic prostate cancer.

 Greg Guthrie: Great. And so what does this mean for patients?

 Dr. Agarwal: From patient perspective, we can see here very clearly that using standardized tools, very validated tools, which have been used in multiple trials in the past, patients are not reporting any adverse impact on their quality of life when being treated with intensified androgen deprivation therapy. In this context, apalutamide.

Greg Guthrie: Great. Alright. So let's move on to our next study, which is, “Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer.” The VISION trial.

Dr. Agarwal: Thank you. In my view, this is 1 of the most important studies presented in the 2021 ASCO Annual Meeting. This study was a phase 3 study where 7,000 patients were recruited, and they had metastatic castration-resistant prostate cancer and had disease progression on a prior novel hormonal therapy such as enzalutamide or abiraterone and the patients had received a taxane chemotherapy. So at least 1 taxane chemotherapy was required before the trial, and the patient had to have disease progression on a novel hormone therapy. These patients were randomized in 2 to 1 fashion to a novel drug, which is a type of radiation, intravenous radiation, as I would explain to my patients, and this is known as beta radiation. And this is a novel radiotherapy where radiation particle, which is delivering beta radiation particle to the cancer cells, is tagged to a molecule, which binds with the prostate cancer cells. So I'm simplifying it for the sake of our patients. And this particle or this compound was added to standard of care therapy and patients were randomized to standard of care therapy versus standard of care therapy plus this new compound. And standard of care therapy was a novel hormonal therapy or anything which did not include chemotherapy or radium 223, which is another type of radiation particle, but a different kind of particle known as alpha particle. So in this study, radiographic progression-free survival and overall survival were primary endpoints. We can see here that the study met both primary endpoints. There was a significant improvement in radiographic progression-free survival with an almost 5 month, 5.4 months, to be precise, improvement in radiographic progression-free survival, with a 60% reduction in risk of disease progression or death. If you look at overall survival, it was also improved in a significant fashion in patients who received the new compound known as lutetium-PSMA-617, and the median survival was improved by 4 months with an approximately 40% reduction in risk of death.  This was a well-tolerated drug overall, and if you look at hybrid side effects, treatment, and emergent side effects, there were 52.7% of patients in the experimental arm, and 38% in the control arm had those treatment-related side effects. So overall, Wwell-tolerated regimen with improved overall survival and radiographic progression. Thank you very much.

Greg Guthrie: Thank you, Dr. Agarwal. This is really interesting, and it will be interesting to see if this treatment does change standard of care based on this research. Let's move on to Dr. Grivas and bladder cancer research. Let's see, so Dr. Grivas, your first study is, “Avelumab first-line maintenance for advanced urothelial carcinoma: analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial.” And Dr. Grivas was a co-principal investigator in this trial and is senior author of the New England Journal of Medicine publication and co-author of this abstract. Go ahead, Dr. Grivas.

 Dr. Grivas: Thank you so much, Greg, and thank you to Cancer.Net for the opportunity, and thanks to the audience. We welcome questions. I would like to update the audience today about the data we saw at the ASCO meeting, and I would like to place this data in context, and I would remind the audience the JAVELIN Bladder 100 trial that changed clinical practice was initially presented last year at the ASCO Virtual Meeting 2020 by Professor Powles. And this particular trial tried to answer the following question: does the immunotherapy, especially the PD-L1 inhibitor avelumab, add value in patients who completed chemotherapy in the first-line setting of metastatic urothelial cancer compared to just best supportive care in terms of longer life, in terms of overall survival, and time until the cancer grows or death, progression-free survival? This is important because until this study came about last year, the practice was, in the setting of spread metastatic urothelial cancer, when the chemotherapy stops, was we cannot give it for a long time because of potential side effects. Usually you used to wait until the cancer grows back, it progresses, or grows. So this trial compared this approach, the best supportive care, versus the immunotherapy with avelumab and the best supportive care. This particular trial, so the significant improvement of life expectancy and overall survival as well as progression-free survival, time until progression of the cancer or death, in the patients that received this immunotherapy drug avelumab as a way to maintain or sustain the benefit that is seen with chemotherapy. So we call this a maintenance therapy approach because we tried to maintain or sustain the benefit with chemotherapy. I want to highlight that this was published in the New England Journal of Medicine and the audience can retrieve that from PubMed if one wants to read the manuscript. The bottom line is this trial changed practice, and we can go now to updates. We saw this in this particular meeting, ASCO 2021, and I think the main question was, are there any particular subsets of patients, different categories of patients, who benefit more from the avelumab maintenance approach, or does this benefit all the patients? And we saw at the ASCO meeting, we saw that the benefit with this immunotherapy appears consistent across the board, across different subcategories of groups of patients. And I think that it's important to point out that we looked at patients who had what we call local disease around the bladder, that was invading this area, and the pelvic side wall that was not amenable to surgical rejection and also patients with spread of the cancer in distant sites, what we call metastasis. And we look at patients who had a primary origin in the bladder or higher up in the urinary tract, what we call kidney pelvis, or ureter, and we call this upper urinary tract, versus the lower tract, which is the bladder, and we also look at patients who had metastatic spread in the lymph nodes only or other parts of the body. And with the bottom line, we saw that the benefit with the immunotherapy was consistent across the different groups of patients. So many patients benefit from this treatment, again, with variable degrees, variable magnitude of benefit, but overall, the bottom line is, take home message is if you have clinical factors or other molecular factors, we do not have a reliable, accurate tool to select which patients should go with avelumab, so we offer it nowadays in every patient who has no contraindication to get immunotherapy and has received some disease control. Meaning a response of the cancer or stabilization of the cancer with the chemotherapy phase. So that has real clinical implications, and I encourage the audience to discuss with their oncologist about the optimal roles of immunotherapy with this maintenance setting after chemotherapy when this is controlled with chemotherapy.

Just for context here, I want to highlight the options the patients have in clinical practice. And when someone is diagnosed with spread urothelial cancer, they can be offered nowadays avelumab as a maintenance strategy to maintain the benefit of chemotherapy, and the other options include immunotherapy up front, like drugs like pembrolizumab or atezolizumab, and I will come back to that question how to select your treatment in my last slide. And I want to point out these are the options, and obviously clinical trials are always a great option for patients, and they should ask their oncologist about those options. So since I talked about immunotherapy, I want to point out that the ideal chemotherapy is cisplatin-based chemotherapy. Not everybody has enough fitness of the body to tolerate cisplatin. For those patients, we think cisplatin may be too much, we use carboplatin/gemcitabine, and we use avelumab maintenance in that scenario. What about immunotherapy after that? Is there data supporting that use? And the answer is yes. There is some data suggesting that immunotherapy can be an option for some of the patients, and in this particular slide, we update the data from another clinical trial. And I will let Greg, you can read the title of that.

Greg Guthrie: Sure, so this study is, “First-line pembrolizumab in cisplatin-ineligible patients with advanced urothelial cancers response and survival results up to 5 years from the KEYNOTE-052 phase 2 study.” Dr. Grivas, you're a co-author on this study.

Dr. Grivas: That’s right, thank you, Greg. This trial presented longer follow up to see what happened in patients who received the immune checkpoint inhibitor anti-PD called pembrolizumab because they were not fit enough to get cisplatin chemotherapy. Keep in mind this was designed before the previous study I showed you presented the results and included patients who were not fit for cisplatin, but some of them could have been fit for carboplatin. There was no comparison here, everybody received pembrolizumab as a single agent, alone, and in this particular study, we would try to see the degree of shrinkage of the cancer and the overall response rate as well as how long people lived over time. So with longer follow-up, by the way, we published this study in the Lancet Oncology years ago, and we have longer follow-up, and what you see here is a degree of shrinkage of the cancer, what we call overall response rate, was about 29% in what we call all comers, and it was higher size of tumor shrinkage in patients with high PD-L1 expression. PD-L1 is this brake of the immune system, the checkpoint of the immune system and highly expressive measured by particular assay that pembrolizumab works better in those patients. However, some patients even with low PD-L1 measured by this CPS score I put in the slide still might have benefits, so the take-home message here is there is a particular proportion of patients who can benefit from the checkpoint inhibitor pembrolizumab. PD-L1 can be used in that setting to help decide between chemotherapy and immunotherapy. However, we have not compared directly the chemotherapy followed by the available maintenance with immunotherapy up front, so this question is still lingering. However, if the patient has a response shrinkage to pembrolizumab, many of those patients may have a long-lasting response. We tried to figure out with research how can we predict who is going to benefit more from this treatment as a matter of ongoing research.

Greg Guthrie: Dr. Grivas, can you really quickly define CPS for our audience?

Dr. Grivas: Absolutely. Great question. CPS is a tool we use in the pathology labs to measure the PD-L1 expression. It can be measured by different assessing antibodies, and the pathologists use a score to define if the PD-L1 is high or low. In this particular study, CPS of 10 or higher defines PD-L1 high expression, CPS below 10 defines PD-L1 low expression, and this appears to have some association with a chance of the tumor shrinking with immunotherapy with pembrolizumab.

Greg Guthrie: Great. Thanks, Dr. Grivas. So our last study is, “Pembrolizumab versus investigator's choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer: 5-year follow-up from the phase 3 KEYNOTE-045 trial.”

Dr. Grivas Very quickly, this study compared immunotherapy, pembrolizumab, the anti-PDL1, compared to chemotherapy with paclitaxel, docetaxel, or vinflunine, the latter one is in Europe, after progression of cancer growth on platinum-based chemotherapy. This was published in the New England Journal of Medicine a few years ago, and pembrolizumab prolonged survival, people lived longer compared to the chemotherapy. And this longer follow-up presented by Dr. Bellmunt and colleagues, showed the sustained results with follow-up, this population of patients had already received cisplatin-based chemotherapy and the cancer progressed, growth, despite that chemo, and in those patients, pembrolizumab appears to produce better results compared to this salvage chemotherapy shown in that slide. And this has implications because immunotherapy can be used in those patients after progression on platinum-based chemotherapy.

And just to wrap up here the discussion, I just want to give the options to the patients, see if someone has a new urothelial cancer, options include cisplatin/gemcitabine, or if someone is not fit enough for cisplatin, carboplatin/gemcitabine, and both of those scenarios can be followed by avelumab, and those with shrinking or stable disease, patients who have progression on platinum-based chemotherapy can get pembrolizumab and of course other options available. We can go into another podcast, and I encourage the audience to look and discuss with their oncologist about those options, and the take home message, the clinical trials is what got us here, and I recommend clinical trials to be discussed with your oncologist. Thank you so much, and I'll be happy to take questions.

 Greg Guthrie: Thanks, Dr. Grivas. So we're going to move on to Dr. Zhang, who is going to talk about kidney cancer. So our first study today is, “Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: a randomized, double-blind, phase III KEYNOTE-564 study.”

Dr. Zhang: Thanks, Greg. I'm really excited to be here today and thanks, everyone, for joining. KEYNOTE-564 was presented at the ASCO plenary by our colleague Dr. Toni K. Choueiri, and this is a highly anticipated study in the adjuvant space for kidney cancer and enrolled patients with high-risk clear cell kidney cancer who had undergone either nephrectomy or a metastastectomy, removing their few sites of metastatic disease and treating those patients with either pembrolizumab for up to a year or placebo. And the endpoint was disease-free survival, and enough events had occurred by this ASCO for us to see the primary results. So the overall -- the study was positive. For the primary endpoint, disease-free survival improvement was met with a hazard ratio of 0.68 and the estimated disease-free survival rate at 2 years was 77% for patients treated with pembrolizumab versus 68% for patients treated with placebo. The overall survival favored pembrolizumab, but it was not yet statistically significant, and follow-up will be needed. Overall, we see an improvement in disease-free survival delaying time until recurrence for patients treated with pembrolizumab, and this was the first study in this adjuvant space showing checkpoint inhibition has a role in adjuvant treatment of renal cell carcinoma.

 Greg Guthrie: Thanks, Dr. Zhang. Our next study is, “Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: results from 42-month follow-up of KEYNOTE-426.”

Dr. Zhang: This study, KEYNOTE-426, we are all very familiar with. Pembrolizumab and axitinib has been used for the last 2 years in the first-line treatment of clear cell metastatic kidney cell cancer, and it's a longer-term follow-up, more events and more understanding of what happens to these patients once they're treated in a longer term, so primary endpoints of course of this phase 3 study were progression-free survival and overall survival. When we're looking at this medium duration of follow-up at 42 months, so about 3 and a half years, pembrolizumab and axitinib improved both median overall survival as well as median progression-free survival. We'd point out that the -- at the 3 and a half year mark, the overall survival rate for patients treated with the combination was about 57.5%. And the progression-free survival rate was about 25%, so about a third of patients had not had progression of disease at 3 and a half years. Which is quite meaningful if they can stay on their first-line treatment for that long. The objective response was 60%, and of note, the complete response rate had been updated to about 10%. So there are some patients that do have delayed complete responses. And no new safety signals were observed. So overall, certainly still provides a lot of evidence to treat with pembrolizumab and axitinib for patients in the front-line setting.

Greg Guthrie: Great. And our last study here is, “Health-related quality of life analysis from the phase 3 CLEAR trial of lenvatinib plus pembrolizumab or everolimus versus sunitinib for patients with advanced renal cell carcinoma.”

Dr. Zhang: This was the phase III trial in first-line treatment of metastatic clear cell kidney cancer that was reported at GU ASCO in February of 2020, and it was a 3-arm randomization to lenvatinib with everolimus in the standard study, and lenvatinib with pembrolizumab or sunitinib alone, and we saw the efficacy data in February, and here we're seeing the quality of life outcomes, and looking at how patients are doing, patient-reported outcomes on these treatments. And so with multiple quality of life measures, we're seeing improvements in patients that had better disease-related scores of symptoms when treated with lenvatinib and pembrolizumab versus sunitinib. We're seeing pain scores improve and patients having less diarrhea, appetite loss, when we're comparing against sunitinib. Of note, it's hard to specifically tie a particular symptom, if that's improved, because they've had better disease control or if it's more from the treatment side effect itself. So still hard to tease out a causality in these quality of life measures, but overall, improvement in patients' quality of life when treated with lenvatinib and pembrolizumab. And certainly provides some more data for patients receiving this combination.

And so I just wanted to highlight our ongoing phase 3 combination trials and first-line metastatic kidney cancer. PIVOT-09 with bempegaldesleukin has completed accrual in the first triplet of COSMIC-313 with ipilimumab, nivolumab and cabozantinib has completed accrual, so the actively enrolling studies currently are PEDIGREE and PROBE. These are studies that are being carried out in the cancer cooperative groups, as well as a triplet belzutifan lenvatinib with pembrolizumab, a study that Merck is running and all 3 very important studies we will continue to learn from and answer some important, clinically relevant sequencing treatment discontinuation, nephrectomy side effect questions. Thanks to everybody.

Greg Guthrie: We have 1 more. So, “Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer.”

Dr. Zhang: Dr. Rodriguez from Spain presented this of papillary renal cell carcinoma treated with savolitinib and durvalumab, and specifically looked at the MET-driven subset of 14 patients out of these 42 patients. The efficacy primary end point was objective response rate. And of note, and median progression-free survival for the 42 patients who were all treated, it was 4.9 months and in MET-driven disease, so savolitinib targets MET, so MET-driven disease was 10.5 months and the median overall survival in everyone was 14 months, versus MET-driven was 27 months, and also higher response rates for patients with MET-driven disease. So I think personally, hypothesis generating, we will likely be seeing more trials with durvalumab and savolitinib in MET-driven papillary renal cell carcinoma.

Greg Guthrie: Thank you, again, Dr. Zhang. And Dr. Gilligan, we're going to talk about some testicular cancer research now, and the first study is, “Testicular cancer in the cisplatin era: causes of death and mortality rates in a population-based cohort.”

Dr. Gilligan: So this study was looking at what happens with testicular cancer patients who are cured of their cancer, are they at risk of dying of other causes? They looked at over 5,000 men treated between 1980 and 2009, so it's important to recognize that some of the treatments given back then are a little different than the way they're given now. And it looked at the risk of death from causes other than testis cancer compared to men without testicular cancer in the general population, and the concerning finding from this study, and it's not the first study to report this, was that the risk of non-testicular cancer death, that is, death from other causes, was increased by about 28% in men who had been treated with radiation therapy and about 23% in men treated with chemotherapy. There's a risk of non-testicular cancer death, the risk, excuse me, was doubled in those whose treatment included both. So it was higher with either radiation or chemo and it was actually 100% higher or double than both those who had chemotherapy and radiation. As you got more chemotherapy, the risk went up. There was no trend towards the increase with just 1 or 2 cycles. We started to see the increase with 3 cycles, and it became statistically significant with 4 cycles. But there wasn't much difference between 3 and 4 in terms of the absolute number that was seen. In terms of death from other cancers, so why is this happening? Other cancers are a major issue after chemotherapy or radiation. Again, the risk was increased 60% after radiation therapy and 43% after chemotherapy, and those who got both, the risk of cancer was 3 times higher than the general population. So that's in men who had chemotherapy plus radiation therapy. Fortunately, there are not a lot of men who get both of those treatments anymore. Non-cancer deaths increased 17% after chemo and 55% of treatment included both. So the risk for non-cancer deaths was not as high as the risk for death from secondary malignancies. Interestingly, the risk of suicide increased 63% in men treated with chemotherapy. That's not affecting as many men as those other numbers, even though 63% number looks high, but it is a concern. Those treated only with surgery did not have an increased risk of non-testicular cancer death. What does this mean for patients? It really means when we can use surgical treatments instead of chemotherapy or radiation as an additional incentive to try do that, and what that may mean is there should be a larger role for retroperitoneal lymph node dissection as an alternative to chemotherapy or radiation therapy. Secondly, for patients getting chemotherapy, it's important to minimize the number of cycles of chemo as long as we're not sacrificing long-term cure rates, because the biggest risk of death is dying from the cancer, but that means limiting to the 3 cycles instead of 4 cycles is probably a good idea, and I think it's an argument to use 3 cycles of BPE instead of 4 cycles of EP because it’s really the etoposide and the cisplatin that is linked to the secondary cancer risk, not the bleomycin, as far as we know. And then lastly, we need to pay attention to the mental health needs of men treated with chemotherapy. That there is more emotional distress and we’re seeing here a higher risk of suicide.

 Greg Guthrie: So our second trial is the, “SEMS trial: result of a prospective multi-institutional phase 2 clinical trial of surgery in early metastatic seminoma.”

Dr. Gilligan: So if we're going to use more retroperitoneal dissection and less chemotherapy or radiation, 1 place to do that is in stage 1 and stage 2 seminoma, and many centers around the country have started doing that, and this was a trial that looked at that approach. So these are men who normally would be treated with chemotherapy, 3 cycles of BEP, or radiation therapy to the back of the abdomen and part of the pelvis potentially. This study looked at the small number of patients, 55 men, low volume, stage 2 seminoma up to 3 centimeters of size and maximum dimension. And what they reported of those men undergoing retroperitoneal lymph node dissection, 10 relapsed, so 18% relapsed after median follow-up of 24 months, they were all alive at the end of the study. No deaths. 8 of 10 relapses were treated with chemotherapy, and 2 were treated with additional [surgery]. Out of the 55 men, 8 ended up getting chemotherapy. Normally, all of them would have gotten either chemo or radiation. Relapse-free survival was 87%, overall survival was 100%.

Seven (7) patients developed complications after RPLND and 5 of them were mild. Two (2) were more severe. So it’s a well-tolerated treatment, if it's done at a large volume center, it's worth noting that the centers participating in the study were large volume centers. Again, if not treated with RPLND, all of these men would have gotten chemo or radiation. The relapse rate after chemotherapy or radiation is about 5%. So the relapse risk is higher after surgery, but in the sense, if we take 100 men with early stage 2 seminoma and do an RPLND instead of chemo or radiation, we can spare 80% of them the long-term effects of chemotherapy or radiation. Alternatively, if the priority is simply to prevent a relapse, radiation therapy and chemotherapy are more effective at that, the relapse risk being 5% but at the cost of long-term side effects from chemotherapy or radiation. Bottom line there is an additional treatment option for low volume stage 2 seminoma for men who prioritize avoiding the complications of chemotherapy or radiation therapy. Both of which are associated with an increased risk of death from other causes. The price we pay for that is the relapse risk is higher with RPLND compared to the other approaches. Not all centers are going to be offering this, but major centers that do a lot of testicular cancer, this is becoming a new treatment option. With the caveat that we have less experience with this approach. This is a relatively small study. And we have a lot more experience with chemotherapy or radiation. I don't think there's a one size fits all here, but I think patients should talk about it with their doctor. If they have early-stage seminoma, they should talk about surgery as an alternative to radiation or chemo.

Greg Guthrie: Here we go. “Surveillance after complete response in patients with metastatic non-seminomatous germ-cell tumor.”

Dr. Gilligan: So this study is looking at the question, if you take a man who has retroperitoneal lymph nodes that are enlarged and metastatic non-seminomatous testis cancer with lymphadenopathy in the back of the abdomen and you put them through chemotherapy and at the end, all retroperitoneal nodes are now within normal limits, normal size nodes, and no bigger than 10 millimeters or 1 centimeter, do we need to do a retroperitoneal lymph node dissection on those patients? Some centers recommend it and some don't. This looked at 388 men in that situation. They were put on surveillance. These men did not undergo the post-chemo RPLND. Two years survival, overall survival was 97.8%. Two-year progression-free survival was at 90%, 34 patients relapsed, and 10 of the men died. Men who did relapse had surgery, chemotherapy, or both as subsequent treatment. There's a prior similar study that was multicenter that had longer follow-up of 5 years, and they reported of ;161 men who had a complete response to the first-line chemo, 10 relapsed (that’s 6%) and none died. If we combine these 2 studies together, the bottom line is you would have to perform a post-chemotherapy retroperitoneal dissection, which is a big operation, on about 550 men to prevent potentially at most 44 relapses and 10 deaths. We don't know if we would prevent or how many of those relapses and deaths we would prevent. But there's a lot of operations with a relatively low yield. In the future, we hope to have blood tests that will tell us which men need surgery. And even right now, we're close to the point that we have blood tests that will detect residual cancer. And the chance is we worry about residual cancer in these patients and we don't have the blood test to pick it up. But the bottom line is in the meantime, the preferred management strategy is surveillance rather than surgery for most men. There's some men for whom RPLND may make sense in the center in this setting and some centers that will probably continue to recommend it for most men. I think this data really casts doubt on whether we ought to be doing this operation in these men as a routine practice as opposed to an exceptional practice for men who have particular characteristics. Thank you.

Greg Guthrie: Thank you, Dr. Gilligan. And now we can move on to answering some questions.

What is the average time expected to see a decline in PSA in patients treated with lutetium-177 PSMA?

Dr. Agarwal: I think this a great question and I think we're waiting for the manuscript published to go through the nuances of those data. Right now, what Dr. Michael Morris from Memorial Sloane-Kettering presented were the high-level data on pre-survival and overall survival and some secondary endpoints. We are anxiously waiting the full data in the form of a manuscript. And until then, I will not be able to answer that question. I would like to add that usually the median time, if you look at how -- for how long patients were receiving lutetium, it was 5 to 6 months. If I -- if my recollection is correct.

Greg Guthrie: Is radiation required prior to initiating chemo if there's tumor presence? And Dr. Gilligan, you responded. “We rarely use radiation therapy for testicular cancer at this time. Sometimes it is used for stage 1 or stage 2 seminoma as primary treatment instead of chemotherapy.”

And I'll just read these aloud for our viewers here. If a patient has both prostate and bladder cancer, how do you decide which therapy should take priority, also, is the CPS typically included on the biopsy report? And Dr. Grivas, you responded, which I'll read here. “This is a bit of a complicated scenario that requires detailed discussion with a urologist and medical oncologist. Regarding CPS, the possible role is only in the first-line setting of metastatic disease to help somewhat decide between chemotherapy followed by avelumab maintenance and immunotherapy. However, it's not a perfect biomarker and not part of the pathology report, it's a special test that requires specific ordering.”

I have a question for you, Dr. Zhang. Why do combination treatments seem to work better in kidney cancer? Wouldn't you have more side effects because you're taking 2 drugs at the same time?

Dr. Zhang: It's an interesting question. You know, our immunotherapy backbones seem to have good treatment benefit for these immune responsive diseases. The VEGF inhibitors that blocked blood vessel formation for many of our patients with clear cell kidney cancer, they tend to have an immunomodulatory role, so if we normalize blood vessels in the tumor microenvironment, the thought is that the T cells and immune cells can actually get into that space more readily. And so many of these blood vessel blockers are hypothesized to have increased immunomodulatory times of behaviors and the combination actually can be more effective than either agent alone, and we've certainly seen that in practice and really excited to see these combination strategies thrive and be standard of care for our patients now and first-line treatment. For the side effect question, you know, I do think that sometimes we do have to tease out which of the side effects is related to the oral treatment, the blood vessel blocker versus the immune therapy. But it's often experienced oncologists who are able to manage these side effects. We can try to tailor and see which of the side effects is due to which treatment and how to reduce or hold treatments when necessary.

Greg Guthrie: Great. I just got a follow-up question for you, Dr. Zhang. Are there any studies for papillary type kidney cancer with sarcoma?

Dr. Zhang: I would assume you're asking about sarcomatoid renal cell carcinoma within papillary, so for papillary type of kidney cancers, there are ongoing studies. For example, with FH mutations and FMH loss. For sarcomatoid disease, this is a special type of histology that can occur with any of our actual histologies of kidney cancer. And we know from our phase 3 trials in clear cell sarcomatoid renal cells that these tend to respond to the immunotherapy combinations. And so I would urge using an immune therapy combination in patients who had sarcomatoid renal cell carcinoma.

Greg Guthrie: Dr. Agarwal, here is a question for you. There were several studies in here that showed many patients did not receive combination ADT with other novel therapies, which you describe as the standard of care, including the one you discussed. Is this something that patients should proactively bring up with their doctors?

Dr. Agarwal: Fantastic question. I'm so glad you asked. The answer is yes: It is our responsibility as physicians and providers, but it doesn't hurt if our patients are educated and challenge us in our decision-making. It is a shared decision-making, it is not the doctor's decision. In my view, it's the patient's decision with help from the doctors. So, yes, please go do it. Doctors usually welcome that.

Greg Guthrie: Great.

Dr. Grivas: I see one for Dr. Gilligan about surveillance imaging that just popped up. [Is there any data on the benefits vs. risks for imaging based surveillance (CT, MRI, none) for longer-term follow-up periods (e.g. 2+ years)?]

Dr. Gilligan: Yeah, they're asking whether there's data on benefit versus risk for imaging-based surveillance and it's actually a very timely question in the sense that we're starting to get data that MRI is very accurate for this. And may likely become a substitute for CT scans at some point in the future. This is something we talk about a lot in terms of surveillance for testicular cancer patients, can we switch to MRI from CT because CT has ionization that can cause other cancers, and MRI does not. The good news is it looks like with current CT scanning, which is lower dose than older CT scanning, the risk of cancer from the CT scan seems really miniscule. Ultimately, it would be great to get it down to 0 and not do them, but we're still doing them. The switch to MRI is being held up by the fact that when you go in and get an imaging study for surveillance, your scans get looked at by a radiologist and also by the oncologist and all of us who do a lot of testicular cancer have multiple stories of catching stuff that the radiologist missed, and they also catch stuff that we miss. It goes both directions, and we're having 2 different people read the films to get a more accurate read. With MRI, most oncologists are not competent to read an MRI well and some radiologists are not great, and the centers where they have excellence have shown that MRIs are just as good as CT scans if read by fully qualified people. And the concern is: are they going to be skillfully read? So the switch to MRI will happen in the future, and I have spoken with people very recently about this that are practicing around the country and the people I talked to were not ready to make the switch because of the concern that stuff might get missed. And I think we can be reassured with the modern lower-dose CT scans, the risk seems to be quite small, and I look forward in the future to making that switch at some point.

 Greg Guthrie: And I think that's going to be our last question this afternoon. Thank you to all our participants for sharing this great research with us, as well as your expertise, it’s been a real pleasure on this live webinar here.

ASCO: Thank you Dr. Agarwal, Dr. Grivas, Dr. Zhang, and Dr. Gilligan.  You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

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This presentation is provided solely for informational purposes. The ideas and opinions expressed in this presentation do not necessarily reflect the views of the American Society of Clinical Oncology (ASCO) or its affiliates. The mention of any product, service, or therapy in this presentation should not be construed as an endorsement of any product, service, or therapy mentioned. The information herein does not constitute medical or legal advice, and is not intended for use in the diagnosis or treatment of individual conditions or as a substitute for consultation with a licensed medical professional. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the presentation or any errors or omissions. © ASCO 2021, all rights reserved.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available.  

Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today’s podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, bladder, and kidney cancer.

This podcast will be led by Dr. Timothy Gilligan, Dr. Neeraj Agarwal, Dr. Tian Zhang, and Dr. Brian Shuch.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Center. He has no relevant relationships to disclose.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for Janssen and Bristol-Myers Squibb.

Dr. Zhang is an assistant professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Janssen and Bristol-Myers Squibb.

Dr. Shuch is the director of the Kidney Cancer Program at UCLA Health and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at the institution. He has served in a consulting or advisory role for Bristol-Myers Squibb.

View full disclosures for Dr. Gilligan, Dr. Agarwal, Dr. Zhang, and Dr. Shuch  at Cancer.Net.

Dr. Gilligan: Hi, I'm Dr. Timothy Gilligan from the Cleveland Clinic Taussig Cancer Institute. I'm joined today by Dr. Neeraj Agarwal from the Huntsman Cancer Institute and the University of Utah and Dr. Tian Zhang from the Duke Cancer Institute and Brian Shuch from the UCLA Institute of Urologic Oncology. Today, we're going to discuss 3 ongoing trials in prostate cancer, bladder cancer, and kidney cancer. As you may know, clinical trial are the way that doctors are able to find better treatment for diseases like cancer. Patient participation is vital for clinical trials. By participating in the clinical trial, you can directly help researchers develop better treatment, reduce side effects, and even reduce the risk of cancer altogether. The 3 trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers Panel from the trials in progress abstracts that were presented at ASCO 2020 Genitourinary Cancers Symposium. Because these are ongoing clinical trials, final results from these studies are not yet available. I'd like to note that none of us have any direct involvement in any of these trials. To view our full disclosures, please visit the show notes for this episode on Cancer.Net. We're going to start with Dr. Agarwal and a study looking at prostate cancer, the MAGNITUDE trial. [A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer (MAGNITUDE)] Dr. Agarwal, can you tell us a little bit about this study?

Dr. Agarwal: This is a large phase III trial of 1,000 patients. This trial includes patients who have progressive, metastatic, castrate-resistant prostate cancer and have never received any other systemic therapy for their castrate-resistant prostate cancer.

Dr. Gilligan: Why don't we clarify for listeners what we mean by castrate-resistant prostate cancer? Who are these patients?

Dr. Agarwal: When patients present with advanced prostate cancer which has [spread] to different parts of the body, that is called metastatic prostate cancer. And the most effective strategy, which is the backbone of treatment of these patients, is androgen deprivation therapy or castration therapy, which blocks the production of testosterone from the gonads. At this point of time, utilizing medical castration [with drugs] or surgical castration can effectively slow down the progression of cancer.

Dr. Gilligan: So these are patients who are already on first-line hormonal therapy to lower their testosterone level?

Dr. Agarwal: Yes. Once they start progressing on this first-line castration therapy, we call this state to be castrate-resistant prostate cancer. So this is the patient population which is having disease progression on first-line therapies for the advanced prostate cancer, and now, testosterone levels are low, but still, the prostate cancer is progressing.

Dr. Gilligan: So what's the current standard of care for this population of patients who are progressing on first-line hormonal therapy?

Dr. Agarwal: In the last 2, 3 years, the treatment of castration-sensitive prostate cancer, which is the newly diagnosed advanced prostate cancer we were just talking about, has changed dramatically. Multiple drugs which are being used, or were being used, in the castrate-resistant prostate cancer have moved to the setting of castration-sensitive prostate cancer. Having said that, many patients with castration-resistant prostate cancer have not yet received any of those drugs. So as an example, in this clinical trial, a patient could have received chemotherapy with docetaxel in the first-line therapy setting or a newly-diagnosed metastatic prostate cancer setting. But then when they have disease progression, the most commonly utilized medications are either abiraterone or enzalutamide, both are oral pills, we call them novel hormonal therapies. So those are still the backbone of treatment for castrate-resistant prostate cancer.

Dr. Gilligan: So for patients going on this study, what would the treatment be on the trial?

Dr. Agarwal: Patients will be randomized to treatment with abiraterone, which is a novel hormonal therapy, plus prednisone, which is utilized with abiraterone to negate the side effects of abiraterone, plus/minus a new class of drug known as a PARP inhibitor. And in this trial, the drug which is being used is called niraparib. Niraparib is a novel drug, a PARP inhibitor, and just to elaborate a little bit more on PARP inhibitors, this class of drug have recently been approved [to treat patients with] the later phases of castrate-resistant prostate cancer. So 2 drugs, olaparib and rucaparib, were recently approved by FDA in those patients who have had disease progression on novel hormonal therapy plus/minus docetaxel chemotherapy, so for pretty late phases of prostate cancer or castrate-resistant prostate cancer. In this trial, a PARP inhibitor is being moved upstream so that patients don't have to wait for disease progression or novel hormonal therapy or chemotherapy in metastatic castrate-resistant prostate cancer, and they will have the availability of this drug upfront in this setting of newly diagnosed metastatic castrate-resistant prostate cancer.

Dr. Gilligan: When this drug is used in the more advanced setting, it's limited to patients who have particular mutations. Is that the case in this study as well?

Dr. Agarwal: This trial is targeting the strategy to 2 different patient populations. So 1 patient population is that [in which the] tumor has defects or mutations in the DNA repair genes. We call them homologous recombination repair mutations. I put it simply, DNA repair gene mutations. So there is a cohort of patients, a group of patients, among these 1,000 patients, who will harbor DNA repair gene-related defects in the tumors. And there is another cohort of patients who do not have to have those defects, and we call them unselected patients. This trial is enrolling both groups of patients, and, in fact, the patients' unselected cohort has actually completed accrual. So the trial is now only looking at those patients who are harboring DNA repair gene-related defects in the tumors. Just to complete the story in this context, as you said, the drugs olaparib and rucaparib, which have already been approved in the later phases of castrate-resistant prostate cancer, they are only approved for patients who are harboring DNA repair defects.

Dr. Gilligan: So for the patients who can go on the trial now, who have these defects, the question this trial is asking then is, does it help to use this treatment earlier on rather than waiting until later?

Dr. Agarwal: Absolutely. So given these are oral therapies, reasonably well tolerated, better tolerated than traditional chemotherapies, it makes sense to move these oral pills to upfront or earlier settings where more patients can be candidates for these drugs which can be taken at home, and these patients don't have to have disease progression on chemotherapy to [receive] these medications. Just to complete, Tim, I just want to add that there are 2 endpoints of this trial. One is radiographic progression-free survival, which is the primary endpoint, and the secondary endpoint is overall survival and many other endpoints we'd like to see, like pain progression or toxicities and so on. Radiographic progression-free survival means how long these drugs or drug combination is able to contain the disease from progressing [or worsening] as detected by the scans. We hope that this trial will show delayed progression on the novel combination compared to abiraterone.

Dr. Gilligan: Thank you. So one last question, are there any known risks that patients should be aware of? What are the side effects of this class of medication?

Dr. Agarwal: Yes. Two major side effects. Every drug has side effect. And so do niraparib and abiraterone. So abiraterone is already approved for patients with metastatic castrate-resistant and castration-sensitive prostate cancer. So I'm not going to elaborate much on abiraterone. Regarding niraparib, this class of drug, including olaparib and rucaparib which I earlier mentioned, they have this class of side effects, which belong to this class of drugs. And 1 of the most common side effects is anemia, which is low hemoglobin, and which happens because these drugs can also slow down the replication of red [blood] cells. Other less common side effects are decrease in the platelet counts and decrease in the white cell counts. But they happen with much lesser degree compared to anemia. Another common side effect is nausea. Nausea and vomiting can happen, and we have to keep an eye on nausea and vomiting because the side effect can easily be prevented or treated with anti-nausea medications. There are many other side effects which are less common, and I won't get into them, but these are the 2 most common side effects, which are fortunately easy to handle in the clinic.

Dr. Gilligan: And I just want to repeat what you said before that there is accrual still going on for the study, but it's limited to patients who have particular mutations in their cancers.

Dr. Agarwal: Yes. So currently the study is not accruing for those patients who do not have those DNA repair general-related events. But it is still accruing patients, looking for patients who are known to have those mutations in the prostate cancer.

Dr. Gilligan: What proportion of patients with prostate cancer have these kinds of mutations?

Dr. Agarwal: Depending upon the study, I would say up to 20% of patients can have DNA repair gene-related defects in their tumors. So it is very important to bring this up with our clinical or medical oncologists who are treating patients with metastatic or advanced prostate cancer, and especially with approval of 2 drugs, it is very important that every single patient who is deemed to be a candidate for treatment with this class of drug, PARP inhibitor, undergoes comprehensive genomic profiling or simply speaking, mutation testing of their prostate cancer tumors.

Dr. Gilligan: Thank you. And I think that's worth emphasizing. This is an example of personalized cancer care based on the genomics of the individual's tumor which is happening more and more, and as Dr. Agarwal said, if you have metastatic prostate cancer, we are recommending a standard of care that people get genomic testing now. So this is an example of a step in that direction. So thank you, Dr. Agarwal.

Dr. Zhang, why don't we move on and talk about the bladder cancer trial that you were going to discuss, the PROOF 302, that also has a personalized genomic component to it, I believe. [Study of Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations]

Dr. Zhang: In bladder cancer, we've come to a place where the genomic profiling is very important to find FGFR mutations or fusions, and this subset of patients that have FGFR mutations or fusions, these patients tend to have good responses to now standard of care treatments in the metastatic setting. And this particular trial is looking at using a drug called infigratinib in this patient population, specifically targeting that FGFR and inhibiting it. This is a trial in the adjuvant setting for patients who have urothelial cancer of either the bladder or of the ureters and upper tract who received surgery and then go onto this trial or treatment with infigratinib versus a placebo.

Dr. Gilligan: Can you spell out for our listeners who the group of patients are who are going to be eligible for the study?

Dr. Zhang: Sure. These are patients who have already undergone surgery for either their bladder cancer or an upper tract tumor. And so these are patients in that 4-month window after surgery, who have already had their surgeries, and it's either for patients who have had prior chemotherapy before their surgeries or not with higher-risk features defined based on each of those populations. But it is for a higher-risk patient population that have a higher risk for having disease recurrence and spread of their urothelial cancers after surgery. In this setting, we really don't have any approved adjuvant treatments. And so the point of this study is really to try to prevent disease recurrence.

Dr. Gilligan: I want to clarify 1 thing. My understanding was for these patients who have not had preoperative chemotherapy, they are not patients who were considered eligible for postoperative cisplatin-based chemotherapy since that is often used in the adjuvant setting. Is that correct?

Dr. Zhang: That's absolutely correct, Tim, and thanks for pointing that out. So if patients had not received preoperative chemotherapy, they have to be ineligible for cisplatin-based chemotherapy, which we would often recommend in the postoperative setting. But if they are not eligible for chemotherapy after surgery and have these higher-risk features, then they would qualify for this study.

Dr. Gilligan: I think it's important for patients to understand that because if considering going on this trial, the standard of care would be just to watch. And so what it's asking is, can we do something instead of just watching that would lower the risk of relapse or worse outcome with the cancer?

Dr. Zhang: Absolutely. I think we always try to recommend proven strategies first, and in this particular case, the recommendation for somebody who is a candidate for chemotherapy after surgery would still be to go with chemo first.

Dr. Gilligan: The genetic testing that will be done to determine eligibility for the study, can you say a little bit more about that?

Dr. Zhang: Sure. My understanding is that the study will take most genomic tests that are currently commercially available, but they have to fulfill the criteria of having FGFR mutations and/or fusions in the tumor in order to go on the study. So we often now will send the surgical specimens for genomic testing, especially in our higher-risk patients that are defined like the study defines. And so that particular patient population, because they're at higher risk for recurrence, we try to identify these FGFR mutations and fusions early on so that we can know whether the standard treatment for these patients would be an option later on.

Dr. Gilligan: Are there cost implications of that for the patients?

Dr. Zhang: Certainly, now some of the commercially available genomic testings are approved by insurance and are billable through insurance, but patients may be responsible for a copay. I want to add 1 more thing about the drug itself because I do think there's some interesting activity of infigratinib that has been published in the last year, and that is in the earlier-phase studies of infigratinib in the metastatic setting, in the more advanced urothelial cancer settings, we saw pretty high response rates as well as disease control rates, particularly in patients who had disease in the upper tracts, so in the ureters and above. And so I think it's promising and potentially very interesting to study this for patients who have had disease removal, and surgeries.

Dr. Gilligan: That's an important point for listeners to understand, that this is an exciting new class of drugs and in patients for whom this treatment is appropriate, we're seeing very good response rates in more advanced disease settings, and there's a natural progression. When we see it work in the advanced setting, we try to move it to an earlier setting to see if we see a similar or greater benefit. As Dr. Agarwal was saying about prostate cancer, we've found a number of times that using drugs earlier works better. This is another example of studying that to see if that's the case here.

Dr. Zhang: I absolutely agree.

Dr. Gilligan: What should listeners know about potential risks or side effects for this class of treatment?

Dr. Zhang: FGFR inhibitors like infigratinib have a class effect, and I think the main toxicities that we've come to see are skin toxicities and nail toxicities, as well as there are some eye toxicities as well. So particularly for patients who are going on these types of treatments, we often will recommend baseline eye exams, and then to follow them on treatment, particularly for any blurry vision or other vision changes that arise. And 1 of the class effects of these FGFR inhibitors is also to cause increases in phosphorus levels [in the blood], and that is due to their inhibition in the renal tubules to prevent phosphorus excretion. And so there was a recent publication also that for patients who develop high phosphorus levels, while getting infigratinib or these FGFR inhibitors, that these patients actually have potentially a higher response rate as well. So I think that has to be proven more in these bigger trials, but it's an interesting biomarker potentially for patients who might have good responses.

Dr. Gilligan: So for patients who had urothelial cancer resected or at high risk for relapse, this is an exciting new option for them, if they have the right genomic composition of the cancer and would not otherwise receive chemotherapy. So thank you for the summary.

Okay. So now we're going to talk about kidney cancer and the CYTOSHRINK discussion. [SBRT With Combination Ipilimumab/Nivolumab for Metastatic Kidney Cancer (CYTOSHRINK)] And we have Dr. Brian Shuch with us to discuss that. Brian, can we start off with who this study is designed for?

Dr. Shuch: It's really designed for patients with metastatic kidney cancer. Could be any type of kidney cancer, presenting with metastatic disease. We call that de novo metastatic disease. So they would have their primary tumor still in place in their kidney, with disease outside of that organ in other locations.

Dr. Gilligan: So these are patients with-- they have the tumor in their kidney, it's spread somewhere else, and they haven't had any other treatment so far? They haven't had any surgery or any drugs?

Dr. Shuch: Correct. These will be patients that are treatment-naïve that are going to start on their first course of treatment, which, in general, would be a discussion of either surgery or systemic therapy.

Dr. Gilligan: So at this point in time, what's the standard of care for such patients?

Dr. Shuch: We used to take every patient to surgery upfront. We call that a cytoreductive nephrectomy. Since we've had much better agents in recent years, and these agents have a lot of activity, we've done less upfront surgery as it appears that some patients may not benefit from racing off to the OR. So these are patients that generally would get started on systemic therapy first because this population, and this trial, has some risk factors for worse disease. We call that intermediate- or poor-risk features.

Dr. Gilligan: So these are patients who we would not normally do surgery on because it doesn't seem to help them, unlike some of the other patients who we do, the good-risk patients.

Dr. Shuch: Well, we are investigating that in other trials, but there are plenty of patients who are not going to run right to surgery, and these are the ones that we would consider deferring surgical management of the primary tumor. We would get started on systemic therapy, and we would reassess how they would be [treated] in the future, whether surgery was an option. But there are emerging entities such as radiation, which we'll discuss, which could be another exciting approach.

Dr. Gilligan: So if a patient that was going to go on this trial didn't go on the trial, they would most likely be treated with medications at this point in time. Is that correct?

Dr. Shuch: Correct. There'd be standard medications which are available off clinical trial which are right now dual therapy with 2 immune agents, or an immune agent and a tyrosine kinase inhibitor. So these are standard drugs that are available off a trial. Patients get started on therapy, and we see how they do later for other treatment options.

Dr. Gilligan: So what is this study looking at? What's the new thing that it's introducing and the question that it's asking?

Dr. Shuch: So kidney cancer, 10, 15 years ago, there was never really any role for radiation except for very rare circumstances. But now we have newer types of radiation where we're doing radiation at much higher doses in shorter time periods, and we call that ablative dosing. And as we've used that in brain and bone lesions for kidney tumors, and with excellent efficacy, with great—what we call local control. That has been applied to the primary tumor as well, and that's been used in many fields, that type of alternative radiation approach. We call that stereotactic radiation or the term radiosurgery, which is really a misnomer. It's just high dose ablative radiation, and it can be used in the primary tumor as a way maybe to kill the tumor.

Dr. Gilligan: And what is that outcome that we're hoping for? How would success be measured if this trial is positive?

Dr. Shuch: Well, we do know for small tumors, it seems to be a fairly effective measure at stopping tumors from growing. In this situation, it's employed after initiation of systemic therapy. Half the patients will get this radiation therapy to that primary kidney tumor, and the goal is to see if it delays progression of the disease. What we call progression is generally growth of lesions that are existing, or development of new lesions, new spots around the body. So the goal is to see if radiation with the standard immune therapy would delay progression versus the standard immune therapy alone.

Dr. Gilligan: So just to reiterate then, I guess for patients who are on this trial, normally they would get treated just with the immunotherapy or combined immunotherapy and targeted therapy, and what we're asking here is, if we give them radiation too, do they do better? Do we delay progression of disease? That we keep things under control longer, that they live longer?

Dr. Shuch: Correct. Obviously, living longer is a major factor. That's another objective of the study, but the study doesn't have enough patients or enough power to kind of detect that. The real issue is, does it delay the progression? And progression is important because if you have progression, often patients will progress to another line of therapy, meaning disease is not under good control.

Dr. Gilligan: Are there any known risks from the radiation therapy the patient should be aware of?

Dr. Shuch: Depending on the size of the tumor and the location to other organs, radiation could have some local effects. Obviously, there's some potential damage to surrounding structures such as the skin. There's some radiation that potentially could stray into other surrounding organs like the duodenum on the right side or the liver, the colon, small bowel, the ureter. And those organs generally can have some degree of toxicity. Generally, it's self-limiting with minor long-term effects, but we haven't done this for many, many years because it's a newer emerging modality. We do believe it's safe with large studies of smaller tumors, but patients do need to be aware that there could be some local irritation from radiation.

Dr. Gilligan: Is this trial still open to patients?

Dr. Shuch: So this is a trial based out of Canada by 1 of their cooperative groups in Ontario. It's a small study - only 78 patients - that opened this year. In discussion with the investigators, this study is accruing well, but it is anticipated to be open for another year. Because they're looking at what's called progression-free survival, we're hoping we can have results of this study within the next 2 years. Obviously, it is something open only to Canadian residents right now, but I will tell you that there are other groups in the U.S. that are considering similar types of trials in the Cooperative Group Network.

Dr. Gilligan: There's 1 final point I wanted to give you an opportunity to clarify for our listeners who may not be familiar with the idea of cytoreductive nephrectomy or cytoreductive treatment. So this is a treatment where we are targeting the primary tumor, even though there's other cancer elsewhere in the body that we can't remove. Can you just talk a little bit about the rationale for that, and why we're doing that?

Dr. Shuch: Historically in kidney cancer, when we had no effective therapy, we would have this phenomena: we removed the big bulky tumor, and 1% to 2% of patients would have their distant sites shrink, okay? And whether that was related to an immunologic phenomenon, maybe the tumor was secreting something, or maybe it was just overwhelming the body's defense mechanisms because they had a big tumor making them sick, it was kind of unclear. But we did know in larger trials with immune therapy, when we gave immune therapy in the old days, the agents like interferon-alpha or IL-2, we gave these agents, the primary tumor wouldn't shrink. Sometimes the distant sites could shrink, but it would not lead to what we call complete responses. So anyone who wanted to have a home run therapy where it was hoping to cure them, they would have their primary tumor removed first, and then they would potentially have the systemic immunotherapy. We've done 2 trials which showed, early in the 90s, that if you were able to remove the primary tumor and treat with these older immune agents, patients would have better outcome. And as those agents were pretty ineffective, we thought the survival benefit was really due to removing the big bulky primary. So the rationale for this trial is, you're not removing the big bulky primary tumor, you're potentially killing it with radiation, so you're overall reducing the burden of disease. There are some theoretical benefits of radiation where you kill tumors, and the tumors release what we call antigens. Basically, I try to explain that to people it's basically like a patch. Like a Boy Scout or Girl Scout has a new patch on them, and you'd recognize them as maybe having a badge of like hunting. So the tumor potentially might expose some of these bad patches, and the immune system might wake up and recognize them, and hopefully, then attack other sites of disease. So, again, the goal is either you're reducing the overall burden of disease in the body, or you're maybe allowing the body's immune system to kick in because you're killing a [tumor] there. We're just not sure really the mechanism, but it's been long used in kidney cancer, this idea of reducing the burden of disease.

Dr. Gilligan: Thank you for listening to this podcast. There are many different clinical trials currently enrolling people with genitourinary cancers. If you're wondering whether participating in a clinical trial might be right for you, please talk to your health care team.

ASCO: Thank you, Drs. Gilligan, Agarwal, Zhang, and Shuch.

Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for.

And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

ASCO: You’re listening to a podcast from Cancer.Net (Cancer dot Net). This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Dr. Fay Hlubocky  and Shelly Rosenfeld discuss what people should know about returning to work after cancer treatment. This podcast is intended for informational purposes only and does not constitute legal or medical advice. 

Dr. Hlubocky is a licensed clinical health psychologist with an expertise in psychosocial oncology and a health care ethicist at the University of Chicago. She's also the Cancer.Net Associate Editor for Psychosocial Oncology.

Ms. Rosenfeld is the director of the Disability Rights Legal Center’s Cancer Legal Resource Center, which provides free information and resources about cancer-related issues. 

View disclosures for Dr. Hlubocky and Ms. Rosenfeld at Cancer.Net.

Claire Smith: Hi, everyone. I'm Claire Smith, a member of the Cancer.Net team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient education website of ASCO, the American Society of Clinical Oncology. Today, we'll be talking about what people with cancer should know about returning to work after treatment, including information about the legal protections available to people with cancer in the United States. Our guests today are Dr. Fay Hlubocky and Ms. Shelly Rosenfeld. Dr. Hlubocky is a licensed clinical health psychologist with an expertise in psychosocial oncology and a health care ethicist at the University of Chicago. She's also the Cancer.Net Associate Editor for Psychosocial Oncology. Thanks for joining us today, Dr. Hlubocky.

Dr. Fay Hlubocky: Thank you, Claire. It's such an honor and a privilege to be with you and Shelly today.

Claire Smith: Wonderful. Our next guest, Ms. Rosenfeld, is the director of Disability Rights Legal Center's Cancer Legal Resource Center, which provides free information and resources about cancer-related legal issues to members of the cancer community across the U.S. Thanks so much for being here, Ms. Rosenfeld.

Shelly Rosenfeld: Thank you. I'm honored and grateful to be here today.

Claire Smith: Before we begin, I should mention that Dr. Hlubocky and Ms. Rosenfeld do not have any relationships to disclose related to this podcast, and you can find their full disclosures on Cancer.Net. So, to start, Dr. Hlubocky, can you talk a little bit about some of the ways that people might think about work differently after an experience like cancer?

Dr. Fay Hlubocky: Thank you, Claire. That's such an important question to start today's talk with. For many, the thoughts and decision-making surrounding returning to work can be very complex. Perspectives on if, how, and when to return to work will differ from person to person. Although one may feel quite motivated and even inspired to return to work after the cancer experience, the idea to return to work immediately after this post-cancer journey phase may simply seem overwhelming and bring about anxious and worrying thoughts. Thoughts and questions such as, "Am I ready to return to work after all I've been through?" or "Can I do the job like I did before?" are common and expected.

For some who may experience financial burdens, these individuals feel compelled to return to work with thoughts of, "I have to get back to work," and feel like that's the only option is to return to work immediately even if not ready. Yet others may ask themselves, "Should I work full- or part-time? How can I return to work?" Or, "Can I return to that same busy schedule as I had engaged in before?"

Finally, some may wonder if that same job is right for them after all one has been through. Again, these are very normal, common, and expected thoughts and questions regarding return to work that the individuals certainly may hold after the cancer experience.

Claire Smith: Wonderful. Thank you for that overview. And next, you touched on some concerns, but I'd love to hear about what concerns someone might have about returning to work after cancer. Let's go to you, Ms. Rosenfeld.

Shelly Rosenfeld: Well, one concern for someone returning to work, it could be either, of course, returning to their job, but it can also be returning to work and starting a new job. And that might be when one might need to perhaps take additional days off, and whether it's for treatment or follow-up care or perhaps just monitoring as well. But to use up those sick days and then to need additional sick days, there is protections out there such as Family and Medical Leave Act, or FMLA. But a concern for someone starting a new job is, in order to be covered by FMLA or the Family and Medical Leave Act, someone has to have worked for the employer for a total of 12 months and have worked at least 1,250 hours in the last 12 months, which comes out to a little more than part-time. But that is certainly a concern because taking time off whether to care-- actually, it could also be a caregiver taking care of someone with cancer, that they need to have worked for that employer for at least 12 months.

Later, I think we might be talking about one way to work with the employer in terms of - just to kind of hint with the Americans with Disabilities Act - kind of a creative way to ask for additional time off and to see if that can work out with the employer. So I want to wait until we talk about that a little more in depth, but I just want to say there is hope and there is something that perhaps can be worked out with your employer if there is that concern. But I just want to say that while FMLA, and just to kind of briefly touch upon it, it allows certain employees to take up to 12 work weeks per year to take care of oneself or certain family members with a serious health condition. For example, that could include a spouse, parent, or child. So it is unpaid, but one's job has to stay open for that person until the end of that 12-week period, and the employer has to keep providing health benefits. So it's something to keep in mind if somebody is returning to work and is at their job now for some time and needs to take those days off. Beyond those sick days, there are protections out there.

But if they're just returning to work and they haven't been at a job for that long, then they should consider, "OK. Maybe the state has additional protections that the federal law does not have," or to think about-- and we'll talk about reasonable accommodations in Americans with Disabilities Act in a bit, I think, as a solution. So with every challenge, I think there is some kind of option, but that is certainly a concern.

Claire Smith: Yeah. Absolutely. I think it's so important to sort of think about these concerns as people are going to worry about them, but there are ways to sort of address and hopefully cope with them. Dr. Hlubocky, do you have anything else to add?

Dr. Fay Hlubocky: I agree, many survivors we know with cancer do desire to return to work. Just recognizing the fact that holding a job provides a routine, a schedule, freedom, income, meaning, it makes us feel fulfilled, it gives us a sense of purpose, and work specifically for survivors can bring a sense of normality, especially after that cancer experience. Yet for others, we know that the thought of returning to work can be very concerning. Folks might be worried over their energy and their endurance and ability to really perform at their job due to continuing or existing cancer-related or treatment-related symptoms, such as fatigue or insomnia or pain. Others may worry about colleagues' attitudes and relationships, concerns and fears over if colleagues will judge them for their appearance or their performance may arise. As well, many survivors question, “How will I be treated?” or “Will they work with me as they did before?” These are also frequent and commonly held concerns by many patients and survivors.

For all survivors, it's important to recognize that this is a new normal, a new phase in this journey post-cancer and cancer treatment that can really bring a new perspective with greater meaning and purpose. This new perspective - really, this growth - can be a motivator and inspire not only you in the work environment but your colleagues as well.

Claire Smith: So talking about maybe some of the things that we can share with our listeners to help assuage some of these concerns that they may have. I want to start, if someone is applying for a new job after cancer treatment, maybe they've been out of the workforce for a little while while going through cancer and its treatment, are there any legal protections available to them during that process, Ms. Rosenfeld?

Shelly Rosenfeld: There are. So I briefly mentioned the Americans with Disabilities Act, or ADA, which is a federal law that makes it illegal for employers with 15 or more employees to discriminate against, and it includes qualified job applicants or qualified employees with disabilities in any stage of the employment process. So that includes the interview process. A lot of people don't know that before someone even starts working, that they do have those protections. So that is really important for someone to keep in mind as they go through the interview process.

So an employer is not allowed to ask about a job applicant's medical history, whether they've taken any leave in the past, or whether they expect to take leave. The only 2 questions related to disability or cancer that employees are allowed to ask are, "Are you able to perform the essential job functions?" and "How will you perform the essential job functions?" So, in order for someone to receive protection under the ADA, they have to be able to do the essential job functions.

For example, without anyone knowing me, I don't have experience playing football. So, I do not have the ability currently to do the essential functions of being an NFL football player, not at this time and not in the past, so far. So, for example, the ADA, no matter what, wouldn't protect me because I can't do those job tasks. But if someone can do the essential functions of a job, right, they're applying for it, hopefully they're able to do those essential functions, if they have cancer or are affected by the effects of cancer treatment, they could be protected. So it is really important to keep in mind during that job application process, the employer can't ask if you're disabled. I know that sometimes they'll have things on the end of an application, but those are optional, right? So someone does not have to answer that, but they can ask, of course, if you can do the essential functions of the job. And so, yeah, I think that's just something to really keep in mind as someone's going out through that process.

Claire Smith: You talked a little bit about the ADA and how we can use those protections. And a lot of people with cancer, they may have mental changes like brain fog or even physical changes, fatigue, or other side effects, long-term side effects of their cancer and treatment, where they might need some accommodations to be able to accomplish those essential job functions that they can do. Can you talk a little bit about what that process looks like to ask for those accommodations?

Shelly Rosenfeld: Just to recap, cancer, the effects of cancer can be a disability under the Americans with Disabilities Act. I know for some people affected by cancer, thinking of the word “disabled” as it relates to cancer might be just a new way to think about it. So I'm only talking legally. So somebody might have been in the best health of their life and been in the best shape and then they're affected by cancer, and then the law may consider them as disabled. So we're talking about disability in terms of the legal definition for the Americans with Disabilities Act.

 So let's talk about reasonable accommodations. So as you mentioned, of course, the effects of cancer can be a disability because they might substantially impair major life activities such as eating, sleeping, concentrating. And so reasonable accommodations can range anywhere from making changes to a physical environment, such as moving file drawers to a more accessible location, or changes to the way that someone works. For example, teleconferences into meetings rather than in person.

Whether an employer has to give someone the type of accommodation they're trying to get depends on whether giving it would be an undue hardship to the employer. Being an undue hardship usually means practically that it will cost the employer too much to give someone the accommodations, so what costs too much really depends on the specific job and the specific employer at issue. So, for example, what might be easy to do for one employer may actually be really difficult for another, but we usually ask for folks to ask for accommodations before their work performance starts to suffer. So if your performance suffers at work, an employer may take negative action against you if they don't know you have a disability or a need for accommodation. So if an employer sees someone sleeping at their desk, they can be fired. So if the employee decides to ask for a reasonable accommodation under the ADA and tells the employer that they have fatigue from cancer treatment and need more frequent breaks due to fatigue before the employer has a chance to see them sleeping on the job, the employee has more protection at work.

It is a personal decision, and I just want to touch upon this because this question sometimes comes up where people say, "Should I talk to my employer or not?" I know, the CLRC, we don't take a position, yes or no. It is completely that person's decision, and I would respect someone either way. So that might on the one side be a little nerve-racking, but it could also on the flip side be reassuring. But there's no wrong choice. It's best to do what is best for that person. I do recommend, however, if you do want to have that discussion with your employer, if you can find someone trusted, whether it's a parent or a friend or just even a doctor or patient navigator, and try to have that conversation, because it can be difficult talking to an employer about that. Even if you feel like you really have a good relationship with that employer, it is still a different type of discussion. And I just want to also mention that it is an interactive process. So suppose someone asks for accommodation, a reasonable accommodation under the ADA, and the employer says, "This is not something that we can do. It's going to cost too much. It's not practical." Then hopefully they come back with something and say, "How about this option?" And then the employee could say, "It still doesn't really help what is the ultimate challenge here. How about this?" And hopefully it's both sides working together in the interactive process. Now, of course, if someone asks for a reasonable accommodation, it may very well be granted in its original request. But just to keep in mind that if an employer pushes back, it is designed to be reasonable for both sides.

And just to give an example, because I think it could be hard when someone says, "It depends on the employer. It depends on the employee." Right? So many people have such different jobs and employers are also so different, but here's an example. Suppose, for example, someone is a cashier, and they have to interact with people. They have to ring them up and take money and work at the cash register, but they're going through cancer treatment. And they're still able to work, but they do need a reasonable accommodation. So, for example, they might ask for a stool to sit between helping people. So if there's not someone else next in line, they can at least sit down. Giving them a separate office with a gold chair might not be reasonable, because they actually have to be there to help folks, but a stool doesn't take too much space, gives someone the opportunity to sit down, could very well be reasonable. So that's just kind of a way to think about it as an example.

And I think the doctor or also patient navigator team can be partners in this. You can ask, "When someone has this treatment, what side effects can I expect? I do this as my job. Have you had patients like this in the past? What are some things that might have helped them?" And you just start that conversation going and also think about your job and how you go about your job and what might help, or how you're feeling and what could really make a big difference. It might be that snacks are not allowed at the desk, but having a snack and being able to eat it can really combat nausea. It can also be more than one accommodation. There might be more than one side effect that needs to be addressed.

So it is something to keep in mind. Be aware of yourself and what helps you ultimately succeed so you can keep having that income, keep having that job, and hopefully keep having that health insurance. Of course, there's the FMLA protections if someone needs to take that time off, but that is something to keep in mind. And because I promised this, I just want to raise it now, is that if someone is not eligible for FMLA based on they haven't worked at their job long enough to qualify and there's no additional state protections that apply, they may be able to ask for some additional time off under the Americans with Disabilities Act beyond their sick days. Saying, "I don't know when I'll get back," and kind of an indefinite time of leave, that might be harder to get approval for as a reasonable accommodation. But saying, "I need X number of days, and then I'll check in with you about that." Or, "I need X number of days," might be something that the employer might be more willing to work with that person. So like I said, there is something to be worked out potentially.

Claire Smith: Oh, wonderful. Thank you for outlining all of that. I think that's really helpful to sort of understand what that process looks like, what maybe some reasonable accommodations are, and the fact that it is sort of an interactive process.

So another thing that Dr. Hlubocky mentioned earlier as maybe being a concern is how to talk to coworkers. Are there questions that coworkers might have after you've been out for cancer treatment, how to manage perhaps uncomfortable conversations. Can you talk about some of the ways that someone with cancer can kind of help prepare mentally for those kinds of conversations, Dr. Hlubocky?

Dr. Fay Hlubocky: Reactions will be different, and they'll vary from person to person, colleague to colleague. Some colleagues will be supportive, know when to ask or not to ask questions, and these colleagues will also try to be helpful with tasks as you return to work. Yet others might be very avoidant because they simply don't know what to say, and that can be hurtful because we all want to feel supported by our colleagues, especially after an experience like cancer. Therefore, it's important for you to prepare and plan on what you want to say before you're returning to work.

Honestly, there's really no right or wrong way to address this, as everybody deals with the cancer experience differently. You may desire to talk openly about the cancer experience, or you might wish to simply move on in order not to be treated differently by colleagues. Empowering yourself by setting boundaries on how to address these questions is key. For example, you can thank your colleagues for their concerns. However, express that, for you, now is not the time or the place to discuss your experience. Remember, you have to feel comfortable and safe in discussing your experience.

Accept help if offered, especially in the initial stages of returning to work. Also, it's important to be prepared that some relationships may change. For example, those who were supportive and close to you before the cancer may distance themselves afterwards. You will learn who you can count on, and that is what's important. If you do feel comfortable, talk to your supervisor regarding any concerns that you may have about returning to work and addressing colleagues' questions so the supervisor can also help prepare the staff as well. But, again, only if you are comfortable. Be sure to check in with your supervisor, especially if you feel that the work environment is not supportive.

Claire Smith: Wonderful. Great advice. And working can sometimes be stressful under the best of circumstances, and especially if you've gone through cancer treatment, you're maybe starting a new job or returning to a workplace. What are some tips for coping with some of those emotions and stresses that might arise?

Dr. Fay Hlubocky: First and foremost, it's talking with your oncology team about when is the best time to return to work given your specific phase in the cancer survivorship journey, as well as inquiring about symptoms that you may have, like fatigue or cancer-related cognitive dysfunction and any other worries or symptoms that may interfere with returning to work. We want to be sure that you're physically healthy to return to work, and be sure to talk to them about any fears associated with working. Remember, we, your cancer team, are here to help you. Also, knowledge is power, and thus education on what is needed or how to return to work after cancer, taking into consideration life changes and symptoms can help to alleviate some of this distress. Also, again, if comfortable, talk to your supervisor about your options and to determine a plan. With the change in work environment, you may have the option to return slowly, gradually to the work environment first, maybe virtually, then part-time with fewer hours and gradually full-time. Again, if comfortable, talk to your supervisor about any time and work accommodations you may feel.

Planning this return to work in partnership with your supervisor can really help you prepare as well as address any worries and anxieties you may hold. If the stress and the anxiety associated with returning to work is just really simply too overwhelming, talk to your therapist to help you plan to return to work. If you're not already connected to psychosocial support, engaging in the service can be a really valuable tool to help you determine your readiness to return to work. A psychologist, a social worker can really help you with preparing and problem-solving and planning when or if returning to work is an option now or in the future. Cognitive behavioral therapy, or CBT, is a research-based psychotherapy that we use that can help to address anxious and worried thoughts that you may have. And the goal of CBT is really to learn to control, challenge, and overcome distressing thoughts and beliefs about returning to work and helps you learn skills to really change your behaviors.

It's also OK to realize that your job is now not right for you. Remember, a comprehensive plan in collaboration with your doctor, potentially your supervisor and psychosocial support, can really help prepare you, empower you as you begin the process of returning to work.

Claire Smith: One other thing I wanted to touch on a little bit is issues around workplace discrimination. If someone is worried that they might face workplace discrimination after cancer, are there any resources available to them, Ms. Rosenfeld?

Shelly Rosenfeld: Yes. If someone believes they've been discriminated against in the workplace or have questions about anti-discrimination protections, first of all, the Cancer Legal Resource Center, or CLRC, we have handouts on our website about someone's right to be free from discrimination in the workplace. Our website is thedrlc.org/cancer, and we recommend that someone speak with an employment attorney to discuss their legal options if someone thinks that they've been faced with discrimination. Someone also might want to file a complaint with the Equal Employment Opportunity Commission, or EEOC. The person can bring a claim for a violation of the Americans with Disabilities Act, or ADA, file a complaint with their state fair employment agency - of course, that depends on the person's state, where they live and work - or file a lawsuit against their employer. So, there's also an organization called the Job Accommodation Network, or JAN, which is a service of the U.S. Department of Labor's Office of Disability Employment Policy, where someone can learn more about resources available to them.

So certainly, there are different options. We hope that no one experiences discrimination because of cancer, their history of cancer, an association with someone with cancer. Hopefully, no one ever experiences that. But if they do, hopefully they feel empowered already that there are options out there for them to assert their rights and hopefully ensure that others in the future will be free from discrimination as a result of cancer in the workplace.

Claire Smith: Thank you for sharing those resources. Absolutely. Do either of you have any final thoughts before I let you go today or anything else you wanted to touch on for our listeners?

Shelly Rosenfeld: I just want to say that, at times, it can be overwhelming, in addition to having a cancer diagnosis, to encounter so many different legal issues that are kind of these non-medical side effects of cancer. And I just want to say that at the Cancer Legal Resource Center, and I know that patient care teams really do care about keeping someone informed of their rights, and so it is important to know that there are rights out there and not to be hopeless about their rights because there might be things that you just never knew were possible. But just by making that effort to learn more about what's out there and what you might be entitled to, whether it's a health insurance appeal, whether if someone has to take a longer time off their job more than a year because of cancer, that there are income replacement options potentially through Social Security, that there are just health insurance options potentially out there for them, that there is hope and it is worth trying. It is worth appealing. And to work with your doctor and medical team saying, "Can you give me a letter? Can you write this for me? Do you have something that you've submitted for someone else for appeal for this medication or for this type of treatment?" And try to seek support in a practical way to stand up for yourself because the results and the upside of doing so are so important.

So I just hope that someone comes away with this knowing-- you don't have to memorize or take notes or be an expert to know this after this podcast, just know that it's out there and that there are resources, and you can learn. And what the CLRC does, we do free. So just to know that there is something out there for them.

Claire Smith: Wonderful. Great message.

Dr. Fay Hlubocky: That's great, Shelly. Thank you. I've learned so much from this podcast. And to all the Cancer.Net audience out there, whether you're a patient or a caregiver or even part of the team, please know that we're here to help you in any capacity. Don't fight this alone, have self-compassion, be patient with oneself. This process does take time, and there's lots of resources here to help you to decide if returning to work is right for you now or in the future. Again, we're here to help you.

Claire Smith: I love that. Thank you. And thank you both so much for sharing your expertise today. It was really wonderful having you, Dr. Hlubocky and Ms. Rosenfeld. Thanks for joining us.

Shelly Rosenfeld: Thank you.

Dr. Fay Hlubocky: Thank you so much. It was an honor and a pleasure to be with you all. Thank you.

ASCO: Thank you, Dr. Hlubocky and Ms. Rosenfeld. You can find more resources and information about life during and after cancer treatment at www.cancer.net/survivorship.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

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Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Brielle Collins: Hi everyone, I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. June 15th to June 21st, 2023, marks the third annual National Black Family Cancer Awareness Week, an initiative led by the U.S. Food and Drug Administration's, or FDA's, Oncology Center of Excellence to increase cancer awareness within the Black community. Today we're going to be talking about cancer disparities in the Black community, the importance of cancer screening and prevention for Black families, and resources available to Black families for support. Our guests today are Dr. Luckson Mathieu and Rea Blakey.

Dr. Mathieu is a thoracic oncologist at the FDA in the Division of Oncology 2. Thanks for joining us today, Dr. Mathieu.

Dr. Luckson Mathieu: Happy to be here. Thank you for inviting me.

Brielle Collins: Ms. Blakey is the Associate Director for External Outreach and Engagement at the Oncology Center of Excellence and leads the National Black Family Cancer Awareness Initiative for the Oncology Center of Excellence Project Community. Thanks for joining us today, Ms. Blakey.

Rea Blakey: Thank you, happy to be here.

Brielle Collins: Before we begin, we should mention that Dr. Mathieu and Ms. Blakey do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now to begin, Dr. Mathieu, research has shown that Black people are more adversely affected by cancer than other racial and ethnic groups in the U.S. Can you describe some of the cancer disparities that exist in the Black community?

Luckson Mathieu: Sure, thank you for that question. Before providing a description, I would like to first define cancer health disparities. The National Cancer Institute, or the NCI, defines cancer health disparities as adverse differences that exist among certain population groups and cancer measures, such as numbers of cases, the number of deaths, cancer-related health complications, and quality of life after cancer treatment. Black and African American people have higher rates of acquiring and dying from cancer compared to members of other races. For many of the most common types of cancer, including breast, lung, prostate, and colorectal, the incidence and deaths are higher among African Americans than any other racial and ethnic groups. Furthermore, despite having similar rates of breast cancer, African American women are more likely than White women to die of this disease. African American men have a prostate cancer death rate more than double than that of men of other racial groups. Unfortunately, my description is a brief depiction of an alarming and expansive reality.

Brielle Collins: Thank you for walking through that, Dr. Mathieu. And thank you, too, for providing that definition of disparities. And Ms. Blakey, can you describe the purpose of National Black Family Cancer Awareness Week and its role in addressing these disparities and raising cancer awareness in the Black community?

Rea Blakey: Sure, happy to. The purpose of the National Black Family Cancer Awareness initiative and the dedicated social media week is to increase cancer awareness in one of the most vulnerable segments of the U.S. population, as you just heard described. OCE's Project Community appreciates ASCO's Cancer.Net involvement, absolutely. We also aim to marshal community-based stakeholders, faith-based organizations, historically Black colleges and universities, Black sororities and fraternities, all of this to increase cancer awareness and to build knowledge surrounding cancer clinical trial participation, as well as minority population donations to national genetic databases for cancer research. So OCE's Project Community is the hub of the social media campaign for the National Black Family Cancer Awareness Week via our hashtag, #BlackFamCan. Project Community's intent is to enlist and encourage a wide array of public and private community-focused engagement entities, organizations, families even, throughout the U.S. and beyond, to support efforts to increase cancer clinical trial awareness. So with a common and concerted mission, organizers are urged to focus their supportive endeavors and activities to occur during National Black Family Cancer Awareness Week. That's also in conjunction with the White House Cancer Moonshot Goals.

Brielle Collins: Wonderful, and it sounds like that hashtag, #BlackFamCan, is a good place for people to go if they want to learn more as the week progresses.

Rea Blakey: Absolutely.

Brielle Collins: Wonderful. And Ms. Blakey, what do you think is most important for Black families to know about their cancer risk?

Rea Blakey: The hashtag, #BlackFamCan, and there's also a tagline that's called “Engaging the Generations.” So we know African Americans have the highest mortality rate of any racial and ethnic groups for all cancers combined and for most major cancers. That contributes to a lower life expectancy, obviously, for African American men and women. And so with that, the real effort here is to get people to talk to their families. All too often, families don't really know their own cancer history, and some find it just too difficult to talk about, especially with older generations who may have associated a stigma with a cancer diagnosis, or those who just don't tell to avoid being perceived as a burden to others in their family. So engaging the generations is one of the key aspects of personal or familial cancer awareness and understanding risk and mapping out preventive strategies and pursuing cancer screening. Not only does it take a village, but it requires every generation.

Brielle Collins: Absolutely. And I want to build on that piece of cancer screening. So Dr. Mathieu, can you talk a little bit about why cancer screening is so important and some of the hurdles that Black families may face in getting regular screening?

Luckson Mathieu: Yeah, absolutely. So cancer screening tests, such as Pap smears, mammogram, low-dose CT scans, and colonoscopy, can help find cancer at an early stage before symptoms appear. When abnormal tissue and cancer is found early, it may be the best time or the more easier time to treat. And treatment may even result in cure. By the time symptoms appear, cancers may have grown and spread, thereby making it more challenging to treat and/or cure. Black people are at the highest risk for cancer deaths. This increased mortality risk may reflect a later stage disease at the time of diagnosis among Black patients. Cancer screening is so important for everyone, especially Black people, because it helps identify cancer early and thereby allows for better clinical outcomes. Regarding the hurdles for cancer screening, I believe the hurdles varies for each family. There may be many complex and interrelated factors that can stand in the way of screening for Black families. Each family should directly address that question of what is in the way of getting appropriate screening for cancer. Identifying and overcoming the hurdles may be the best way to address this cancer screening disparity.

Brielle Collins: Got it. Thank you for walking through that. And in terms of resources, Dr. Mathieu, what resources are available to help Black people access this screening?

Luckson Mathieu: So your primary care physician can serve as a good start to discover cancer screening resources. Earlier this year, the Department of Health and Human Services announced the Accelerating Cancer Screening Program. The program's goal is to accelerate access to cancer screening as part of the Cancer Moonshot Initiative. I would encourage everyone to go online and consider the role a local HRSA-supported health center can play in the process of getting screened for cancer. In addition, NCCN.org, CDC.gov, American Cancer Society, and the FDA are great online resources to obtain more information on cancer screening.

Brielle Collins: Perfect. And I really want to talk about that cancer prevention piece, too, which is another incredibly important element of this. So why is cancer prevention in particular so important, and what measures can Black families take to prevent cancer?

Luckson Mathieu: Yeah, cancer prevention is important because the best treatment for cancer is to prevent it from occurring at all or catch it at the earliest and most curable stage. In addition, cancer prevention offers the most cost-effective long-term strategy to manage cancer’s devastating societal impact. As previously mentioned, screening tests can find cancers early when they are treatable and it has the prospect of cure. In addition to regular screening tests, everyday behaviors such as not smoking cigarettes, maintaining a healthy weight, and being vaccinated against certain cancer-causing viruses can all help prevent cancer from developing.

Brielle Collins: Thank you. And Ms. Blakey, going back to some resources, what resources are available to help Black families as they navigate cancer screening and prevention?

Rea Blakey: Well, I'll start with the prevention aspect first. The Centers for Disease Control and Prevention, the CDC, has great resource information for reducing cancer risk. Anyone can share the web page links or even print out materials to hand out to their communities. There's information on the importance of family health history and cancer, on the correlation between alcohol consumption and cancer, cancers related to obesity, smoking cessation resources. And often these resources are culturally curated to meet the needs of a variety of communities, including African Americans, Latinos, LGBTQ. For resources to help families navigate cancer screening, I would recommend that all Americans become familiar with the recommended cancer screening tests that are listed on the National Cancer Institute webpage. It's specific to screening tests. So along with becoming aware of the cancer screening possibilities, you would also want to find a health care provider that you trust. We know trust is a huge issue. And ask questions to help you understand the best cancer screening plan for you. NCI's resource, for example, recommends you ask questions like, are any cancer screening tests recommended for me and which ones? And what's the purpose of the test? Does the test require preparation? How do I do that? These are questions you should be comfortable asking your health care provider and know more about so that you are well equipped to do as much as you can, to make sure that your screening options are actually taken advantage of, and that you do what you can to reduce your risk. You might also want to ask, how often should I have the test and at what age should I stop having that test?

Brielle Collins: Got it. Thank you for that. And I know we touched on this earlier in the podcast, but I just want to circle it back here with National Black Family Cancer Awareness Week. But where can people go online throughout this week? We mentioned that hashtag, #BlackFamCan, but are there other resources available during the week that people can go to online?

Rea Blakey: Absolutely. We have a webpage and a dedicated social media toolkit. So anyone who uses an online search engine and looks up National Black Family Cancer Awareness should see our webpage. On that page, you will find all kinds of resources that include, for example, in the social media toolkit, videos and graphics, as well as a customizable selfie frame for those who are, please do use the hashtag #BlackFamCan. Thank you.

Brielle Collins: Wonderful. It sounds like it's going to be a very engaging week. Thank you for that. And thank you both so much for your time and for sharing your expertise today, Dr. Mathieu and Ms. Blakey. It was so great having you both.

Rea Blakey: Thank you, Brielle!

Luckson Mathieu: Thank you very much.

Brielle Collins: For more information, you can view this podcast on Cancer.Net, where you can also find a link to all the resources mentioned around National Black Family Cancer Awareness Week.

ASCO: Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Every year, the ASCO Annual Meeting brings together attendees from around the globe to learn about the latest research in the treatment and care of people with cancer. This year, a record 42,750 attendees from 138 countries worldwide gathered virtually for the ASCO20 Virtual Scientific Program, held Friday, May 29 through Sunday, May 31.

In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, “What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?” In this first episode, 3 editors discuss new research in the fields of leukemia, colorectal cancer, and lung cancer.

First, Dr. Jessica Altman will discuss 2 studies in myelodysplastic syndromes and acute myeloid leukemia. Dr. Altman is Associate Professor of Medicine in the Hematology Oncology Division at the Feinberg School of Medicine, Northwestern Medicine. She is also the Cancer.Net Associate Editor for Leukemia.

View Dr. Altman’s disclosures at Cancer.Net.

Dr. Altman: Hi, everyone. My name is Jessica Altman. I am a leukemia physician at Northwestern Memorial Hospital in Chicago, and I am pleased to talk today about some interesting studies that were presented at ASCO 2020 and really use that as a marker of the excitement that is ongoing in the field of myeloid malignancies. In both myelodysplastic syndrome and acute myeloid leukemia, there have been a lot of novel therapies that have been recently approved, and other agents that are currently ongoing in a clinical trial. I think it's important for me to mention that the studies that I will be discussing today, I do not have any direct conflicts of interest, but I am involved with the development of other novel therapies. I'll be talking about two studies today. The first one is a clinical trial, and the second one is a palliative care study that was conducted.

The first study that I would like to discuss is the study presented in an oral session at this year's ASCO presented by Dr. David Sallman on behalf of his group at Moffitt and a large clinical trial network of other investigators. They studied the combination of a novel agent called magrolimab, which I'll mention more in a moment, in combination with a standard lower-intensity chemotherapy called azacitidine. This is studied for the treatment of high-risk myelodysplastic syndrome and acute myeloid leukemia. Magrolimab is an antibody that blocks something called PD47, which is a macrophage immune checkpoint and essentially a signaling cancer that says, "Don't eat me." And this antibody allows the engulfment or destruction of tumor cells and also is able to eliminate the really deep stem cells that cause the development or maintain the leukemia and MDS. So in this study, the investigators conducted a trial of azacitidine in combination with magrolimab, and they treated a handful of patients with both myelodysplastic syndrome and acute myeloid leukemia. And what they found was that the combination therapy was both well tolerated and resulted in a better-than-anticipated response rate. So better than what we would anticipate with a low-intensity chemotherapy alone. In particular, they found a nice response rate in individuals whose leukemia or MDS expresses a specific mutation. That mutation is called TP53, and that mutation has been associated with a poor chance of response to the available therapies and particularly a short duration of response.

This trial is particularly exciting to me because it demonstrates the ability to combine novel therapies with lower-intensity treatments and allows what we hope for will be a higher chance of response. This is with a relatively limited study, and further trials in this space involving this agent and combination are planned and are ongoing. There are other agents that are also targeting the TP53 mutation, and those are things to watch out for as well.

I'd like to move on to a supportive care study that was presented as well. This was a study that was presented by Dr. El-Jawahri, and funded by the Leukemia and Lymphoma Society. This is a study that looked at patients with acute myeloid leukemia receiving intensive chemotherapy. The relevance and importance for the study is because supportive care trials, and particularly looking at palliative care in general in acute myeloid leukemia have not frequently been done to date. And the background for this study is that individuals with acute myeloid leukemia frequently can experience decline in their quality of life and mood during their hospitalization for induction therapy. And it is not uncommon for adults with acute myeloid leukemia to receive aggressive care at the end of life.

So this group sought to examine the effect of an integrative palliative and oncology care and affect quality of life, mood and symptoms associated with things like post-traumatic stress and with a huge emphasis on end-of-life outcomes. And what this group found was that the integrative palliative and oncology care model for patients with acute myeloid leukemia receiving intensive chemotherapy led to improvements in patients' quality of life, their psychological distress and the care at the end of life. And the investigators asked for consideration of palliative care as a standard of care for all adults with acute myeloid leukemia, from really thinking about the incorporation of palliative care model, from diagnosis and throughout treatment and not just reserving that to the end of life.

Thank you for your time. I was very excited with the numerous clinical trials in the myeloid neoplasm space presented at this year's ASCO. And the work that was presented is really a marker of how much excitement there is that's ongoing in this field. Thank you.

ASCO: Thank you, Dr. Altman.

Next, Dr. Jeffrey Meyerhardt will discuss 4 studies in colorectal cancer. Dr. Meyerhardt is the Douglas Gray Woodruff Chair in Colorectal Cancer Research, Clinical Director and Senior Physician at the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute, Deputy Clinical Research Officer at the Dana-Farber Cancer Institute, and Professor of Medicine at Harvard Medical School. He is also the Cancer.Net Associate Editor for Gastrointestinal Cancers.

View Dr. Meyerhardt’s disclosures at Cancer.Net.

Dr. Meyerhardt: Hi my name's Jeff Meyerhardt from the Dana Farber Cancer Institute in Boston, Massachusetts. I'm going to speak about some of the key abstracts that were presented at this year's virtual ASCO meeting in 2020. I have no pertinent disclosures related to the abstracts I'm going to discuss. So the first and probably the most prominent and abstract, which was presented in the plenary session, was a study called KEYNOTE-177. It was a study specifically for patients with a certain subtype of metastatic colorectal cancer, what's called microsatellite unstable tumors. It's a way that colorectal cancers first emerged when they developed from normal cells to abnormal cells. It only constitutes about 3 to 5 percent of metastatic colorectal cancers. But we know a lot about those cancers because some of them are related to inherited conditions and some are not related to conditions, but they land up at those other cancers that seem to be much more susceptible to immunotherapy. And in fact, they're the ones that immunotherapy indicated for in terms of colorectal cancer.

And so the study that was presented was comparing patients receiving what's called a checkpoint inhibitor and a type of immunotherapy, in this case, pembrolizumab, to standard chemotherapy. So chemotherapy that we would typically give as initial treatment for metastatic colorectal cancer. Currently, the indication with the FDA is that patients would receive immunotherapy later as a later line of therapy, if other things weren't working and this was really to say, should we be giving it much earlier on?

So as a randomized trial, it was about 300 patients and they compared starting just with an immunotherapy, pembrolizumab versus chemotherapy and either a drug called bevacizumab or a type of a another inhibitor called an EGFR inhibitor, cetuximab.  And it lands up starting with the pembrolizumab had a real significant improvement in progression free survival. It was a comparison of actually 8.2 months with standard treatments, which is what we see in a lot of trials versus 16.5 months. That's essentially for the times we had to switch to different therapy and all these other endpoints were also met in terms of a 12-month and two years of progression free survival. It was a statistically significant event, and it really will change practice for that subpopulation of patients with metastatic colorectal cancer. What's still really important is to try to figure out for the rest of the patients how immunotherapy can benefit them. And that unfortunately, we don't have as much data yet.

Another abstract presented this year at ASCO was a sort of update of what's called the BEACON trial, and this is, again, another subgroup of colorectal cancers, colorectal cancers that have a particular mutation in them, what's called a BRAF mutation.

We know that occurs in somewhere between 5 and 10 percent of colorectal cancers. They can sometimes be a more aggressive cancer and there were multiple drugs that have been tested in multiple combinations of those drugs over the past 10 years, but the largest effort was really looking at trying to give patients a standard treatment to combining a BRAF inhibitor, in this case, encorafenib, which is an oral pill, with an EGFR inhibitor called cetuximab and also potentially adding a third drug, binimetinib, which is called a MEK inhibitor, also an oral pill. And the study, the BEACON study, which was a large international randomized study compared those three arms. The main comparison was saying, should you have two drugs compared to control or three drugs compared to control, control being standard treatment. And looking at both of those compared to standard treatments. They weren't actually meant to compare the two to three drug and initially the results suggest that three drugs was optimal. But the study that was presented at ASCO and ultimately actually led to the actual FDA approval, is using a two drug combination. So encorafenib and cetuximab, which again was better than control and really becomes the standard for later line treatment of BRAF mutated colorectal cancer. We don't know if that should be the initial treatment. That study is now about to get started to say, "Should we start with BRAF directed therapy?" but we know that if you had progressed in other standard treatment, that is certainly an option that should be considered.

There were two studies that looked at adjuvant therapy for colon cancer. Adjuvant is after someone has surgery and then they receive chemotherapy to reduce their risk of recurrence, one of them was a follow up to an effort to look at how many months of adjuvant therapy is necessary. This was called the IDEA collaboration. It was an international effort that included 14000 patients randomized to three months of treatment versus six months of treatment. And what we learned from that is for patients, particularly, who have a better risk tumor. So they all have stage III disease. Meaning they had surgery, the pathology showed some lymph nodes in the sample, but they didn't have evidence of metastatic disease at the time when they were diagnosed and those patients that they received three months of therapy if they only had one to three positive lymph nodes or not all the way through the bowel wall. Three months of therapy seemed to be just as good as six months, particularly when you do a combination of oral drug capecitabine with an IV medication called oxaliplatin and those with higher risk disease, those patients should probably receive six months, though in some cases, three months also seems to be sufficient. And this was a follow up to show that actually overall survival also was not inferior to do three months versus six months in those patients who have better risk disease or with capecitabine and oxaliplatin.

The second adjuvant trial was one that I actually led. It was a large trial that was run through the National Cancer Institute. It was looking at standard chemotherapy in stage III colon cancer, same population I just discussed, and whether adding celecoxib, which is what's called a Cox-2 inhibitors. It's kind of like aspirin, a little bit more specific. And then there was a lot of data that those type of drugs could be helpful in patients to reduce polyps and may potentially be beneficial in patients who already had colorectal cancer. So we conducted a large clinical trial, comparing standard chemotherapy with the celecoxib or standard chemotherapy alone. And unfortunately, adding the celecoxib didn't actually add any statistically significant benefit. There was a slight improvement, but it wasn't statistically significant. So it is a negative study and unfortunately does not move the field in terms of improving outcomes for patients with stage 3 colon cancer. There are still some ongoing studies, specifically looking at aspirin that we await to see if that would make a difference in outcomes. So those are some of the highlighted studies focused on colon and colorectal cancer from ASCO this year. Thank you very much. And again, my name's Jeff Meyerhardt from the Dana Farber Cancer Institute.

ASCO: Thank you, Dr. Meyerhardt.

Next, Dr. Jyoti Patel discusses 3 studies in non-small cell lung cancer. Dr. Patel is the Medical Director of Thoracic Oncology and Assistant Director for Clinical Research at the Lurie Cancer Center of Northwestern University. She also serves as Associate Vice Chair for Clinical Research in the Department of Medicine. She is also the Cancer.Net Associate Editor for Lung Cancer.

View Dr. Patel’s disclosures at Cancer.Net.

Dr. Patel: Hi. My name's Jyoti Patel. I'm a professor of medicine at Northwestern University and associate editor of Cancer.Net for lung cancer, and I'm going to talk about some of the most exciting lung cancer abstracts that were presented at the 2020 ASCO Annual Meeting. One of the most important and, I think, impactful to patients and practice-changing studies was actually selected as a plenary session abstract, and plenary abstracts are those that are rated the highest of all of the thousands of abstracts that are submitted, so whenever there's one in our particular disease site, we're always really excited, and we've been waiting for this ever since we heard from a press release that a positive study on lung cancer was going to be presented. The study was called the ADAURA study. And the ADAURA study was sponsored by AstraZeneca, and I have worked as a consultant for AstraZeneca in the past.  So the study was looking at a drug called osimertinib, in patients who had early-stage lung cancer which was surgically resected. So as we know, a minority of patients, unfortunately, have stage I and stage II lung cancer, and about 30% of patients have stage III lung cancer. For many of these patients, surgery is the primary modality, and we do surgery with curative intent. However, despite doing surgery, there is a significant chance that the cancer can recur.

So the study was looking at osimertinib as adjuvant therapy in patients with resected lung cancer. Osimertinib is an EGFR tyrosine kinase inhibitor. It's a targeted therapy that blocks the EGFR protein, which is often mutated in patients with lung cancer. So osimertinib is the treatment of choice for patients with advanced lung cancer that harbor an EGFR mutation. That mutation occurs in about 15% of American patients, and higher proportions of patients in some parts of the world. These patients, early on, had surgery, and then they were found to have an EGFR mutation, and then they were randomized to either three years of osimertinib as a daily tablet, versus a placebo, and the endpoint of this study was disease-free survival, so that's the length of time until there's evidence that the cancer has recurred. In this study, taking osimertinib significantly reduced the chance that the cancer would return within those three years, and the magnitude of benefit was highly significant. So with higher stages of disease, the likelihood that the cancer could come back is higher, and so the benefit was greatest in patients with stage 2 and stage 3 disease, and in fact, in patients with stage 3 disease, it decreased the recurrence rate by almost 85%. So really, really significant and impactful to our patients.

Some people have questions about whether this should now be a standard of care, because we're not really showing whether we're improving the overall survival of patients. Many oncologists, myself included, think that survival with no evidence of disease is really meaningful for patients. It's going to be important, as the study matures, to see what the overall survival data look like, but in the three years of taking the drug, which is relatively well tolerated, the survival benefits, to me, translates to better quality of life, return to function and work, and staying away from catastrophic complications of cancer recurrence, like cancer coming back in the brain, or in the bone, and really impacting quality of life.

And the next study I want to discuss is a study looking at immunotherapy and chemotherapy in patients with non-small cell lung cancer. So the study is called 9LA. It's a CheckMate trial, so BMS studied their drugs nivolumab and ipilimumab in combination with chemotherapy. My institution has received research funding from BMS for the study of nivolumab and ipilimumab, and I've served as a consultant in the past. In this study, patients who were treatment-naive, so hadn't received prior therapy, were randomized to either chemotherapy, which was an older standard, admittedly, versus a combination of a short course of chemotherapy, so only for six weeks, in combination with the immunotherapies nivolumab and ipilimumab. The rationale for giving chemotherapy with immunotherapy is multifold. So one is that chemotherapy kills cancer cells, and in doing so, it releases neoantigens, or proteins, that might make the immunotherapy more effective. It sort of targets these cells as foreign, and it kind of helps amp up the immune system. It also sort of decreases the cancer burden, and we know that immunotherapy tends to be more effective when there's fewer sort of volumes of cancer to treat. So this was a really interesting design, and impactful because the chemotherapy is given for such a short course, so the ongoing toxicities of chemotherapy over several months, it sort of goes away. So less fatigue, less lowering of blood counts.

The study was looking at overall survival, and the study was positive, and this led to an FDA approval in May. The study showed that, in the initial time in which chemotherapy and immunotherapy were given, patients did quite well, and then they sort of plateaued, and at 12 months, almost two-thirds of patients were on the immunotherapy, compared to about half of patients which were on chemotherapy. And so that was significant. Although these results are comparable to other treatment options we have with ongoing chemotherapy and immunotherapy, are in patients with really high PDL numbers of immunotherapy alone, I think this trial is important for patients because it offers a different alternative. Having a short course of chemotherapy may make a lot of sense for patients. The cumulative toxicity from chemotherapy, it can't really be understated. Although our chemotherapies are better tolerated than ever before, the idea of just six weeks of chemotherapy and then going into immunotherapy, I think, is really an attractive one, and may give us options from multiple other treatments down the line. So I think this is important for patients. I think it certainly makes life a little bit more complicated for medical oncologists because now we have multiple options to discuss with patients, but at the end of the day, that's the best way we can personalize therapy for our patients, really taking into account overall disease status, as well as patient preferences, and tolerance of toxicities, and aims in the future.

The last study that I want to highlight is a study called the DESTINY study. I don't have any disclosures for this study. This study was looking at a subgroup of patients with lung adenocarcinoma with HER2 mutations. So there have been a lot of targeted therapies that have gained our attention and FDA approvals in the past couple of years, and it's really exciting. We're understanding that development of targeted therapies is based on early assessment of mutations in our patients, and we have a host of mutations, now, with FDA approved drugs. Just in May, drugs targeting RET, or R-E-T fusions was approved. Another drug targeting MET exon 14 skipping mutation was approved. HER2 mutations represent a subset of patients, a small subset of patients, about 2% of lung cancer patients, and they've been really difficult to treat. We know about HER2 because it's often a target for breast cancer, but in lung cancer, it's often a small mutation that causes activation, that causes the cells to grow. We haven't had a lot of really great options for these patients, and although there are multiple drugs in development, this particular trial gained a fair bit of attention because it looks quite promising.

So this study was looking at trastuzumab deruxtecan, and that's an antibody-drug conjugate. So the idea is it's an antibody that binds to HER2-- which is on cancer cells. When it binds to that target, the drug conjugate, or the payload, is released into the cancer cell. So there's less toxicity. It's a targeted therapy with very sort of directive toxin to the cancer cells. There are a number of antibody-drug conjugates in development, and some are FDA approved for other indications. In this study - it was a single-arm study - patients with HER2 mutations received the antibody-drug conjugate, and they saw a really significant response rate. Almost all patients had some disease diminution, some response, with about 60% of patients having what we call a partial response, a 30% reduction in tumor cells. What was also exciting was that some patients have been able to show that their responses are quite durable, and so the disease control has lasted. Certainly, this is an early trial. Only about 39 patients were treated. So we look forward to further studies of this compound, but finally, it's nice to have something that looks this promising in this particular patient population.

ASCO: Thank you, Dr. Patel. Learn more about the research presented at the ASCO20 Virtual Scientific Program at www.cancer.net/blog, and subscribe to Cancer.Net podcasts on Apple Podcasts or Google Play for additional episodes in the Research Round Up series, released throughout the summer.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, the Reverend Jane Jeuland discusses what people with cancer should know about the role of chaplains in cancer care, including how chaplains are trained, the type of support they can provide for people with cancer and their family members and caregivers, and how someone with cancer can ask for spiritual support from their health care team.

Ms. Jeuland received her Masters of Divinity from Yale Divinity School. She is an ordained Episcopal priest. She received her chaplaincy training from Yale New Haven Hospital and is a board-certified chaplain. She has served as an oncology chaplain and was the first palliative care chaplain at Yale New Haven Hospital. She has no relevant relationships to disclose. 

Jane Jeuland: Hi, my name is Jane Jeuland, and I am the palliative care clinic chaplain at Yale New Haven Hospital. I'm here today to talk a little bit about what I do at Yale New Haven Hospital, and also, what is a chaplain? What is it that we offer and provide? How are we trained? And some other questions that people have for us as chaplains.

So I'll start by just describing a little bit about what I do at Yale New Haven Hospital in my role. In addition to seeing patients in our clinic, I visit with patients one-on-one through video platforms, phone, and I also visit with patients in person for scheduled appointments. And in those appointments, we get to know each other, we build a rapport and a relationship. And I help people process how they make meaning, find purpose and belonging in their lives, and how that is impacting their cancer care, but also how their cancer is really impacting their meaning, purpose, and belonging. In addition to those individual meetings, I also visit with patients in group settings. I host several groups over Zoom where patients get to talk to one another and share deeply and support each other.

And last but certainly not least, I also have started a podcast with my patients called In the Midst of It All, which you can find on Apple Podcasts and Spotify. And in that podcast, patients share their stories that they've written about their lives, about their cancer journey, and about their spirituality, and how that has helped them through all that they're going through.

So, how do chaplains get trained? I think this is one thing that people ask me quite a bit. What is your training like? Our training is pretty extensive. We need to have a 3-year Master's degree, typically a degree of divinity. And then after that, we have a year of training called Clinical Pastoral Education, CPE for short. And in that year of training, we are with a cohort of about 4 to 5 other chaplains in training. And we are supervised by a highly trained supervisor as well who has quite an extensive and long process to get certified to do that. And what our supervisors do is they help us really go out, visit with patients, and then reflect on those visits. We do things called “verbatims.”

So what is a verbatim? When we write up a verbatim, we're writing up word for word an interaction that we have with a patient. And obviously, we will keep the patient confidential. But we do this with our group and with our supervisor to really kind of drill down and see where are the places that we are inserting ourselves, our own beliefs, our own needs, and how can we really better meet the patient where they are? We talk a lot about positive use of self so that we become really aware of our own self in the midst of our interaction with patients. And over the course of the year, we really learn how to focus on the patient's spirituality, their beliefs, their values, what they need in that moment.

And we're all about helping people discover their spirituality and their faith. I think sometimes a lot of people think that we might be coming in to convert someone or to make them believe a certain belief system or a certain religion. But actually, we're really here to help any patient and caregiver really figure out what it is that they believe, and how that's impacting their cancer care or how their cancer is impacting their beliefs. So that means that we do visit with people of all different faiths. We visit with people who are atheists and agnostic as well. And really, again, just try to help people discover, what is that value that you have? What are your beliefs? Where do you find meaning, purpose, and belonging?

And so what are some things that come up as we meet with patients? I, again, work in palliative care in the clinic settings. I'm outpatient. But a lot of chaplains work inpatient in a variety of settings. And so you'll have chaplains in a medical intensive care unit (ICU), or you'll have a chaplain in an infusion suite or on a floor as well. And so we see patients at all different stages. We see patients who are just newly diagnosed and have a cancer that's highly treatable. We see patients who are doing really, really well on their treatments. And we also see patients who are starting to kind of struggle with lots of symptoms, pain through sometimes months or years of cancer treatments. And then on the other end of this spectrum, we see patients who are very advanced in their cancer, have a terminal diagnosis, and we really see them through all that that entails, the outpatient visits as well as the inpatient, and even as someone comes to the end of their lives.

And so what can come up in our meetings as I meet with patients? When someone's diagnosed with a terminal diagnosis, there is a lot of discussion about fear of dying, what happens in the process of dying, and then also, of course, what happens after we die? What is there after we die? Is there anything after we die? Or what is the afterlife like? And so often, again, I try to help people really reflect on what they may think the afterlife is like, if there is one. And then we have rich discussions around that. For kind of that big question of what happens as we're dying, that's when I like to pull in other members of the team. But certainly, chaplains can help process that as well. We also really do help people articulate their thoughts about the divine and whatever name they give to the divine. And often, what I hear in my appointments is not so much, “Is the divine as God giving me this cancer?” but, “Why would God allow it?” So as I talk with folks, folks will say, "I really believe in a loving God and a God that heals and a God that helps us. Why would a God like that allow me to have this cancer? Why would God allow my loved one to have this cancer and for their lives to be taken far, far too soon?" And for that, it's a tricky one. We, as chaplains, don't have a pill that we can give you and send you home and say, "OK, here's your prescription. Take that, and you'll get all the answers to why would God allow this?"

So it's really a process of talking through this. It's a process of kind of discovering a little bit more about what we believe God is, what the patient believes about God, and God's character in the midst of it all. And it's also just sitting in the mystery of it that we don't know. We don't know why a loving God would allow this, why a God that heals would heal some people and not others, why a God who heals would heal at this point in your life, and then not at a different point in your life, and why this happens at all. And so chaplains don't rush quick to give advice. We allow sitting in that grief, in that suffering, in the sorrow.

But then again, as we talk about who is God for this person, I also like to help people see, OK, if God isn't healing right now, if we can't understand why God is allowing this to happen, where is God in the midst of it? And this is what I love about my job so much is that I hear from such a variety of faiths and people of different values and spiritualities, how they do see the divine working in their lives. And so for some, "I have a lot of pain, but I know that God is with me, and I don't feel alone in this." Or, "I was feeling grief and loss over a loved one and wondering what my afterlife's going to be like as I face the end of my life and I was having this turmoil. And all of a sudden, I felt this deep, deep, deep peace wash over me. And I feel like that might be God." Or for someone who maybe doesn't have a particular religion, they may say, "I know that the love of my family and friends is so powerful. It's helping me through this. It's getting me through the dark times. And I know that that is what holds us together. And it's more than just what we can see and taste and feel, that that love is something greater and bigger." So it's really rich conversations like that that I get to have.

I think also some other topics that come up is cancer is grueling. Cancer, it can be long. And there are things, people talk about scan anxiety. Of course, the side effects and physical pain. I hear a lot about insurance and how that's just so difficult and such a struggle to get on the phone, talk about insurance when time is so precious and so short. And for others who are healing from cancer, it sometimes is a lot of conversation about, "Well, how do I get back to life? And I used to do this amazing job, but I don't think that I can do that anymore. I don't have the stamina. I don't know how I would be able to do that job." And so I help people process that a lot. And again, that goes back to how do we find purpose in life, that meaning, purpose, belonging. And a lot of us find our purpose in work, in what we do. And so chaplains can help people through topics like that as well.

And for survivors, we're always so happy in our palliative care clinic to help people heal. A lot of people think palliative care is just end of life. It is not. I have a lot of survivors I meet with, and they'll talk about kind of always looking over their shoulder. Is it going to come back? And finding a way to give back and to help other patients. And that is something I really love helping people with is, how do we give back? What are some ways to help others after I've had cancer? How can I help people?

And so I have to say, I've been really, really privileged in my work as I meet with patients and individually in groups and help them write their stories and read their stories and interview on the podcast. I've just been so, so struck by all of the beauty, the resilience, the strength that I hear, the really depth and the richness of people's spirituality as they go through cancer care and really do some hard work to unpack and process all that's going on. And some of the common themes that I've heard is people will talk about how cancer has completely changed their perspective. And so people will talk about how before they had cancer, they were focused on their wonderful job, but also the pay and making sure they get ahead and can have stuff, that newest car or that bigger home. And when they have come through cancer and all that that entails, they start to think, "Gosh, you know what? I like those things, but what's much more important is the people that are right in front of me. It's the things that are free. It's time. It's talking with a loved one. It's really sharing deeply what's on your heart and mind, knowing that time is precious."

And so I really am so struck by some of the things that people will share with me about their loved ones, their caregivers. If you are a caregiver, you know that you are loved, and that everything you're doing is really helpful and so, so appreciated, and that the time that you spend together and the things that you're able to share is so important. It doesn't have to be a big trip or people think about bucket list things, and it doesn't have to be all that. It's sometimes just that conversation over coffee or as you're going to sleep at night, those words that are shared are so important. And so people's perspectives, I think, really do shift and change and deepen. And people also find God in the midst of everything that they're going through.

I had a patient who heard stories on the podcast and said, "I really want to write my own." So we worked together. And we talked a lot about her faith, and she wasn't really sure what to believe. She had had a hard time growing up in terms of her spirituality. And through her writing, and also through her cancer journey, she was able to really articulate her sense of God as a loving companion to give her peace, not one that's punishing, but a God that's loving. And now, as she comes to the end of her life, she's really finding a great more deal of peace, thinking about God and knowing that God is with her. I think as I share stories like these, though, I'm always so mindful, too, that I think in our culture, we think a lot about things being 5 easy steps. You can do this, and you can get better, and you can find insight and meaning in 5 easy steps. And it's really not that. It's really a process. And so as you hear stories from other cancer patients who may be in that place of peace and accepting and belonging and you're not there, also know that they were not there at a certain point and that it is a process, and it does take time. And so, again, that's what chaplains are really here for. We're here to help unpack a lot of that, to help people process that.

And so you might be actually wondering, "You know what? I am going through a lot of cancer care here where I am, and I really would actually like to talk to a chaplain. How do I do that?" So the best way is to simply ask for a chaplain. We're most often called chaplains, but sometimes we're called spiritual counselors, spiritual care providers. So maybe a different term where you're located. But you can ask a nurse, your oncologist, anyone on the team, your social worker, to contact a chaplain. There are different levels of care in different settings. So you may have a chaplain in an outpatient setting, but maybe not. And so most likely, most hospitals have inpatient chaplains. If you are outpatient, though, and you really want to talk to a chaplain, I still encourage you to ask for one. And in that case, call the spiritual care or chaplaincy department directly, and you should be able to do that through your information line in your hospital. But in the hospital, for the most part, the hospitals have inpatient chaplains. Many have 24/7 on-call chaplains. And so always don't hesitate to ask the nurse, and we're happy to come by.

We also do provide support for families. And so this is something that we do quite often, especially in the inpatient setting, in an ICU setting, at those times when decisions are being made. What should we do? What we often call in our hospital setting “goals of care” conversations. What is the goal of care here? Are we going to continue with aggressive interventions? Are we going to start to move to aggressive comfort care? And so chaplains help talk through that as well. So you can always call or ask for a chaplain when you're inpatient, certainly when those decisions are being made. And we're there for you as a patient, but again, we're also there for your caregivers, your loved ones. And in those settings, we're often meeting with families sometimes outside of the room even. And we help your loved ones process as well. Just like I've mentioned, all the other things that I help patients process, we also help caregivers with a lot of those topics. In addition, of course, for a caregiver, we sit with them in the pain and the suffering and the loss and the anxiety, and talk through their ways that they find meaning, purpose, and belonging, and how they're processing all that's going on with their loved one, who's the patient.

I've heard from more than one patient that they say, "I feel like as hard as cancer is, it's easier on me than it is on my loved one. I hate to see what they're going through. I sometimes feel like a burden." But whenever I talk to a caregiver about that, they always say, "Absolutely not. You're not a burden. I wouldn't want to be anywhere else in the world." If they're sitting there in the ICU, long hours, surviving on coffee, very little sleep, lots of interruptions, sleeping in a chair beside your bed. Every single time, those caregivers will say, "I would not want to be anywhere else in the world. I want to be here. This is what I want to be doing." If you're the patient, feeling like a burden, know that more often than not, your loved one is really wanting to do what they're doing.

But caregiver burnout is real, too, especially if your care is going on for a long, long time. And so chaplains can help caregivers process that burden. And we also work with the team, sometimes social workers and others to find support systems so that if they need help, so that they can just have a moment to themselves, go for a walk, that we can help them think about resources that may be their faith community, their church, their synagogue, their mosque, their faith community can come and help give that relief or that respite for them, but also other resources in the hospital. So you may have an integrative medicine component.

So I hope that you've been able to learn a little bit more about chaplains, about how we're trained, about what we typically hear from patients, and what we can provide support around. How we also support caregivers. We are inpatient, we are outpatient, we are 24/7 most often, and how you can get in touch with a chaplain. I really encourage you to reach out to a chaplain. We're always happy to help. It's what we're here to do. So thank you so much for having me on the podcast today. It was really a delight to be here. And I hope you have peace. I hope that you find strength, meaning, purpose, and belonging in the midst of it all.

ASCO: Thank you, Ms. Jeuland. Learn more about the role of chaplains at www.cancer.net/palliative.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

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ASCO: Usted está escuchando un pódcast de Cancer.Net en español. Este sitio web de información sobre el cáncer es producido por la Sociedad Estadounidense de Oncología Clínica, o la American Society of Clinical Oncology en inglés, la organización profesional líder en el mundo para médicos que atienden a personas con cáncer.

El propósito de este pódcast es instruir y brindar información. Esto no es un sustituto de la atención médica profesional y no está previsto que sea utilizado para el diagnóstico o el tratamiento de afecciones individuales. Los invitados de este pódcast expresan sus opiniones, experiencias y conclusiones. La mención de cualquier producto, servicio, organización, actividad o terapia no debe considerarse como aval por parte de la American Society of Clinical Oncology. La investigación sobre el cáncer que se analiza en este pódcast está en curso; por lo tanto, los datos descritos aquí pueden variar a medida que la investigación avanza.

Leslie Zhang: Bienvenidos al podcast de Cancer.Net. Soy Leslie Zhang, una escritora en el equipo de Cancer.Net. Como recordatorio, Cancer.Net es un sitio web de información para los pacientes por ASCO, la Sociedad Estadounidense de Oncología Clínica. Pueden encontrar más episodios del podcast Cancer.Net en nuestro sitio Cancer.Net/blog/podcast. Hoy hablamos sobre la evaluación geriátrica integral y su utilidad en el cuidado de las personas con cáncer. Nuestro invitado hoy es el doctor Enrique Soto, un oncólogo clínico que se especializa en el cuidado de los adultos mayores con cáncer. El doctor Soto trabaja en el Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán en la Ciudad de México. Es un miembro nuevo de la junta directiva de ASCO y miembro de la junta editorial de Cancer.Net. Bienvenidos al podcast de Cancer.Net, doctor Soto.

Dr. Enrique Soto: Hola, ¿qué tal Leslie? Muchas gracias por invitarme a este podcast, es un verdadero placer estar aquí.

Leslie Zhang: Gracias. Voy a empezar con las preguntas. Primero, ¿qué es una evaluación geriátrica integral? ¿Que necesitan saber los pacientes sobre la evaluación geriátrica integral?

Dr. Enrique Soto: La evaluación geriátrica integral es una herramienta que utilizan los geriatras, que son los médicos que se encargan de atender a los pacientes adultos mayores, para evaluar a los pacientes de una forma multidisciplinaria, que permita conocer todas las cosas que están sucediendo con esa persona. O sea, es como una consulta médica usual, pero tiene el extra de que se evalúan cosas que son particularmente importantes en las personas mayores. Y la idea es que a través de esta consulta, se logre una visión general integral de las capacidades funcionales, el rendimiento físico, el estado nutricional, las diferentes enfermedades que tienen las personas, la capacidad cognitiva, o sea, la memoria y la capacidad para pensar, el estado psicológico, estado de ánimo y las condiciones de apoyo social y financieras de las personas mayores. Entonces, a través de una serie de preguntas, de cuestionarios y de herramientas que ya están diseñadas desde antes, se evalúan todas estas características de las personas mayores y con eso se logra un entendimiento holístico de la persona en el que todos los aspectos se consideran, y esta evaluación permite encontrar cosas que no se encuentran normalmente en la consulta normal de un oncólogo, en la que se ven algunas cosas y aquí se ven cosas adicionales.

Leslie Zhang: Perfecto. ¿Por qué es importante una evaluación geriátrica para un oncólogo para su tratamiento del cáncer de los pacientes?

Dr. Enrique Soto: Normalmente, las valoraciones oncológicas incluyen valoraciones de la capacidad funcional de las personas, pero suelen ser cosas muy sencillas y unidimensionales. Y eso no necesariamente es lo mejor para las personas mayores, conforme la gente va envejeciendo todos nos volvemos muy diferentes entre nosotros. Y, después de cierta edad el número de años que tiene la gente nos dice muy poco sobre quién es realmente esa persona y qué cosas realmente están sucediendo en su vida. Entonces todos conocemos personas mayores, mayores de 70, mayores de 80, que son extremadamente activas, que son muy independientes, que hacen muchísimas cosas en su vida diaria, y a lo mejor conocemos personas más jóvenes que necesitan ayuda de los demás, que no pueden valerse por sí mismos. Y esto es mucho más importante que el número de años que tiene la gente, y la forma de detectar estas cosas que pueden hacer las personas, es a través de la valoración geriátrica. Entonces, la valoración geriátrica nos da una idea de la verdadera edad biológica de las personas. Y en oncología en particular, nos puede ayudar a predecir la expectativa de vida de los pacientes, a ver qué tanto riesgo tienen de tener toxicidad por los tratamientos, particularmente por la quimioterapia. Y una cosa extremadamente importante es que nos permite encontrar otras cosas que pueden andar mal y en las que al hacer intervenciones, podemos mejorar el estado general de las personas. Si a través de la valoración geriátrica encontramos que las personas están mal de ánimo, que tienen problemas para caminar, que necesitan ayuda social, podemos intervenir en esas cosas y mejorar la calidad de vida global de los pacientes.

Leslie Zhang: Perfecto. ¿Y cómo afectan el tratamiento de un paciente los resultados de una evaluación geriátrica?

Dr. Enrique Soto: Hay muchas formas en las que los resultados de la valoración geriátrica y la intervención de un oncólogo geriatra o de un geriatra, pueden modificar o afectar los tratamientos. Entonces, la evaluación lo que nos puede ayudar es a descubrir vulnerabilidades adicionales que no se detectan normalmente en la historia clínica. Y eso puede hacer que nosotros, durante y después del tratamiento, hagamos intervenciones que estén encaminadas a mejorar estos problemas. Por ejemplo, otra cosa para la que sirve muy bien o para la que se utiliza mucho la valoración geriátrica es para predecir qué tanto las otras enfermedades de los pacientes afectan el tratamiento del cáncer al calcular la expectativa de vida de la gente, y eso nos puede ayudar a tomar decisiones difíciles con los pacientes. A veces, nuestros tratamientos tienen riesgos que pueden superar los riesgos de las enfermedades. Entonces, eso nos ayuda a poner las cosas en la balanza. Y también, y esto es un área de estudio en oncología geriátrica, podemos utilizar la valoración geriátrica para identificar a aquellos pacientes más vulnerables, que tienen más riesgo de tener complicaciones en los tratamientos, y en los cuales hacer algún ajuste en los medicamentos, que puede ser reducir la dosis, cambiar el tipo de medicamentos que utilizamos, puedan hacer que los tratamientos se toleren mejor y se completen de mejor forma. Y hay otras cosas más, por ejemplo, si encontramos que los pacientes tienen problemas de la memoria o problemas cognitivos, podemos ayudarlos mejor a tomar decisiones, apoyándonos además en su familia. Todo este tipo de cosas nos ayudan a que la toma de decisiones compartidas entre los pacientes y los médicos sea más efectiva y que podamos hacer tratamientos que resuelvan el problema de los pacientes causando el menor daño posible.

Leslie Zhang: Sí. ¿Y tiene usted ejemplos de otras enfermedades que pueden afectar el tratamiento del cáncer?

Dr. Enrique Soto: Claro. Una enfermedad muy importante que puede afectar el tratamiento del cáncer, y que es muy común en las personas mayores, son los problemas cognitivos, la demencia. Entonces, con el paso del tiempo, muchos pacientes mayores desarrollan problemas de memoria y problemas de la atención y de la capacidad de toma de decisiones. Y de hecho eso es una cosa para la que mandan muy comúnmente a los pacientes mayores a las consultas de geriatría o de oncología geriátrica. A través de la valoración geriátrica se puede determinar qué pacientes tienen limitaciones para la toma de decisiones, y en esos casos determinar qué tanto ofrecer tratamientos potencialmente tóxicos, es una cosa que le haría más daño que beneficio al paciente. Entonces, esto es una cosa extremadamente importante que hace la oncología geriátrica, detectar los problemas cognitivos. Otra cosa muy común que normalmente no se toma en cuenta en las consultas de oncología es la presencia de caídas. Las personas mayores con cáncer tienen más riesgo de caerse, y al caerse pueden, por ejemplo, fracturarse la cadera, y esto tiene consecuencias muy importantes, tanto para la supervivencia como para la calidad de vida. Entonces detectar de forma temprana que los pacientes tienen riesgo de caídas puede hacer que evitemos algunos medicamentos que aumentan ese riesgo y también que implementemos intervenciones para evitar que las personas se caigan, como por ejemplo, darles un bastón o adecuar su casa para que sea más segura o enviarlos a terapia física o a terapia ocupacional para que ese riesgo disminuya.

Leslie Zhang: ¿Y hay otras cosas que las personas mayores con cáncer puedan hacer para adecuar su casa?

Dr. Enrique Soto: Bueno, en los Estados Unidos, particularmente, existen algunos servicios que ayudan a que las personas mayores adecuen su casa. En otros lugares del mundo esto no es tan común, pero sí evitar que existan obstáculos en la casa, en algunos casos los pacientes tienen mucho riesgo de caídas; evitar que los pacientes tengan que subir y bajar escaleras para llegar a su cuarto; utilizar auxiliares de la marcha, como por ejemplo, bastones o andaderas. Es importante que las prescriba un rehabilitador que seleccione el auxiliar de la marcha apropiado para cada paciente. Y también, mejorar la nutrición y mejorar la fuerza física, todo eso puede disminuir el riesgo de caídas. Y para esto, existen en la mayoría de los centros de cáncer, equipos multidisciplinarios que pueden ayudar a esto. Prácticamente todos los centros de cáncer en los Estados Unidos tienen equipos de fisioterapia o de terapia ocupacional que pueden ayudar mucho para que esto no pase.

Leslie Zhang: ¿Y es posible que los pacientes les pidan que sus oncólogos le hicieran una evaluación geriátrica si no es parte de la evaluación estándar?

Dr. Enrique Soto: Bueno, yo no diría que la valoración geriátrica no es parte de la valoración estándar. Yo creo que hoy en día en todos los pacientes adultos mayores, se debe de hacer una valoración geriátrica antes de empezar el tratamiento para el cáncer. De hecho, desde el año pasado la Sociedad Americana de Oncología, ASCO, publicó las guías para el cuidado de los adultos mayores con cáncer. Y parte de las recomendaciones es que en todas las personas mayores, antes de empezar un nuevo tratamiento para cáncer, se haga una valoración geriátrica y se revisen ciertas cosas específicas: La función física, la memoria, el estado de ánimo, el estado nutricional. Entonces en realidad esto es algo que todos los oncólogos deberíamos de tener en cuenta, que en las personas mayores necesitamos ir un poco más profundo y evaluar estos aspectos a través de la valoración geriátrica. Y además, es algo que se puede hacer en una consulta normal. Hay varias demostraciones de que esto se puede hacer en un lapso de tiempo no muy largo, y que nos da un montón de información que es muy útil para las personas mayores. Entonces yo creo que sí. Los pacientes mayores deben pedirle a sus oncólogos que los vea un geriatra o un equipo geriátrico si es que este está disponible, por supuesto, en el centro donde están los pacientes.

Leslie Zhang: Parece que las valoraciones geriátricas integrales son una herramienta importante para los oncólogos y son esenciales para determinar el mejor curso de tratamiento con menos efectos secundarios adversos. Gracias por su tiempo hoy, doctor Soto.

Dr. Enrique Soto: Muchísimas gracias Leslie por invitarme y espero que esto haya sido de utilidad para los pacientes y para sus cuidadores. Muchas gracias.

ASCO: Encuentre más información de confianza para personas con cáncer en www.cancer.net/es. Y si este pódcast fue útil, tómese un minuto para suscribirse, dar una calificación y escribir una reseña del programa en Apple Podcasts o Google Play.

Cancer.Net está respaldado por Conquer Cancer, la fundación de la American Society of Clinical Oncology que financia la investigación de vanguardia sobre todos los tipos de cáncer para ayudar a pacientes de todo el mundo. Para ayudar con la financiación de Cancer.Net y programas similares, haga su donación en conquer.org/support.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

The theme of the 2023 ASCO Annual Meeting was “Partnering With Patients: The Cornerstone of Cancer Care and Research.” From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting and explain what it means for people with cancer. In today’s episode, our guests will discuss new research in gynecologic cancers [2:06], multiple myeloma [9:15], and head and neck cancer [16:03].

First, Dr. Lan Coffman discusses new research in ovarian cancer, uterine cancer, and cervical cancer. Dr. Coffman is a physician-scientist and gynecologic oncologist at the Magee-Womens Research Institute and Foundation, and assistant professor in Hematology-Oncology at the University of Pittsburgh School of Medicine. She is also the 2023 Cancer.Net Associate Editor for Gynecologic Cancers.

You can view Dr. Coffman’s disclosures at Cancer.Net.

Dr. Coffman: Hi, my name is Lan Coffman. I'm a physician-scientist at the University of Pittsburgh. I'm a medical oncologist that specializes in gynecologic cancers, and I'm happy to discuss research that was presented on gynecologic cancers at the 2023 ASCO Annual Meeting. I do have a relevant disclosure. I participated in one of the trials I'm going to discuss, a trial called MIRASOL. I was the site principal investigator at University of Pittsburgh.

I think there were a lot of interesting studies to highlight, and I wanted to focus on studies involving ovary cancer, endometrial cancer, and cervix cancers as the main sites that we study in the gynecologic oncology world. So when we talk about ovary cancer, I think there was one really impactful study that was presented at ASCO this year, and it was called MIRASOL. And again, this is the study that I also participated in at our hospital at University of Pittsburgh. So it was a large study, so a randomized phase 3 study looking at a drug called mirvetuximab, which is an antibody-drug conjugate.

So basically, it's an antibody against a protein that is expressed on ovarian cancer cells and the protein’s called folate receptor-alpha. And that antibody basically carries a little poison. And so it's kind of like a Trojan horse. This antibody goes, finds that protein on the tumor cells, and then delivers that poison. And so this drug has been studied and actually was presented last year in a different trial called SORAYA, which showed that it had activity, meaning the drug helped to kill ovarian cancer cells, and actually led to the first approval of this drug in ovary cancer. So this trial was the confirmatory trial, so enrolling more patients to see, actually, is it better than standard-of-care chemotherapy? So this was in women with ovarian cancer that had come back and was platinum resistant, meaning the cancer started to grow within 6 months from the last platinum-based therapy. Women were eligible if they had high expression of this folate receptor-alpha, and they had to have a couple of prior lines of therapy.

And then they were randomized, so kind of chosen out of a hat to either be treated with mirvetuximab or with investigator's choice chemotherapy. So one of the chemotherapies we'd use standardly. And so that would be something like taxol, or liposomal doxorubicin, or topotecan. And basically, this study was comparing how well does mirvetuximab work compared to chemotherapy. And importantly, it showed that it improved survival, both progression-free survival, so how long it took before the disease started to grow again, but probably more importantly, actually improved overall survival, so how long a woman lived. And actually changed overall survival from about 16 and a half months compared to 12 months with chemotherapy. And so this was really important and demonstrated that mirvetuximab does actually impact women with ovarian cancer and actually helps women live longer. And that's really hard to do in this setting.

And the other nice thing about this trial was that not only did it work well, but there are actually lower side effects with it, and so less women actually had to discontinue their treatment, and they had less what we call adverse events, or basically bad things that had happened from the treatment themselves. So just telling us that this drug is actually well tolerated. Women feel well on it, even when their cancer is shrinking. So I think that was one of the most impactful studies in ovary cancer. Moving on to endometrial cancer. We recently had 2 studies, one called RUBY and one called GY018 that looked at using immunotherapy in combination with chemotherapy in endometrial cancer. And what was presented at ASCO was some follow-up from this RUBY trial, which was basically validating that this combination of adding immunotherapy actually helped. To give you a background, traditionally, women that have endometrial cancer that is advanced staged, meaning spread outside of the uterus itself or has come back, we treat it with chemotherapy.

But this study added an immunotherapy called dostarlimab in combination with our standard chemotherapy and actually showed that women were living longer with this, at least in that progression-free survival. We're still waiting on final evaluation. But at ASCO, what they reported was another independent blinded review of the data to show that even when we're really carefully looking at this data, it looks like immunotherapy helps women with endometrial cancer live longer. They also presented quality-of-life data showing that women actually feel better with the addition of the immunotherapy. So I think this is practice changing. And again, this data has been coming out over the last year or so, but I do think this will change the way in which endometrial cancer is treated.

And then the final thing I wanted to discuss would be in cervix cancer. And while there wasn't a lot of new data presented here in terms of kind of paradigm shifts or large changes, we did have final survival [data] from the KEYNOTE-826 presented, which is also using immunotherapy along with chemotherapy in cervix cancer. And so this was in women that, again, had advanced-stage cervix cancer. So it was a cervix cancer that had moved beyond the cervix itself or cervix cancer that had come back and was treated with chemotherapy along with another immunotherapy called pembrolizumab. And this was the final survival data that confirmed that the immunotherapy did help women live longer. The survival data was impressive with about a 10-month improvement in overall survival. So how long a woman lived. And so that was really confirmatory of the previous trials. So again, that emphasizes that immunotherapy is moved towards the standard of care in cervix cancer as well. I can't hit all the highlights of the impressive research coming out of ASCO 2023, this is a brief summary of some of the critical studies in gynecologic cancers.

ASCO: Thank you, Dr. Coffman.

Next, Dr. Sagar Lonial discusses new research in multiple myeloma. Dr. Lonial is a professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University, where he also serves as Department Chair. He is also the 2023 Cancer.Net Associate Editor for Myeloma.

You can view Dr. Lonial’s disclosures at Cancer.Net.

Dr. Lonial: Hello, I'm Dr. Sagar Lonial from the Emory School of Medicine and the Winship Cancer Institute in Atlanta, Georgia. And today I'm going to discuss some of the really exciting research in the context of multiple myeloma that was presented at the 2023 ASCO Annual Meeting. In terms of my conflicts of interest, I have enrolled patients on many CAR T trials as well as bispecific trials from all of the different companies involved here. So, I do have some engagement with those trials. And one of the studies that I may talk about at the end came from our institution. So I was an investigator on that study as well.

When I think about some of the really exciting work that was presented at ASCO this year, there are really 2 big categories of trials that I think were most exciting. And the first is CAR T-cells and moving them earlier and earlier in the disease state. And what we saw at ASCO this year was the CARTITUDE-4 study, which was a randomized phase 3 trial comparing CAR T-cells versus standard treatment in the context of first or second relapsed multiple myeloma. And this was a really important study for us to hear because we know that CAR T-cells are highly effective in the later lines of therapy. A big question at this point is, "Does their efficacy hold up in earlier lines of therapy? And how does it compare in a randomized setting against what we might normally use in that clinical context?"

And what I think we were really excited to see at ASCO this year was that CAR T-cells appear to be superior to standard treatment in the context of that randomized phase 3 trial. Now, there were a few patients who were randomized to CAR T-cells who didn't get to the CAR T-cell infusion because their disease progressed in that interval. And that is a challenge that many of us deal with on a regular basis when we think about using a CAR T in a patient. But in general, the treatment was available for almost all patients. And the analysis of benefit as measured by a longer remission duration for the patients who received CAR T cells versus those who didn't was really done on what we call an intent to treat basis. And what that means is if you were randomized to the CAR T arm, even if you didn't get the CAR T, which again was a very small number of patients, you were still evaluated as if you got a CAR. And what I think that tells us is that even taking into account some of those patients who may not get there, there still was significant clinical benefit.

And this is really important data for us to have insight into. We've seen this with cilta-cel in CARTITUDE-4. We'd seen similar kinds of findings in KarMMa using ide-cel as the CAR T-cell, although it does appear that the remission duration, at least when you're comparing across trials, appears to be a little bit longer for cilta-cel than what we've seen with ide-cel. But nonetheless, it suggests that even in the context of early relapse, there may be some benefit for CARs over standard therapy. Now, does this mean that CARs are going to replace standard therapy in terms of early relapse? I don't think we know the answer to that right now. I think there's a lot of information that we need to look at to really feel comfortable making that step.

The other big set of data I think that we were all very excited about to see at ASCO this year were the T-cell engagers or the bispecifics. And what we saw from a number of different bispecifics was that the efficacy data looks like it continues to hold up. But what to me was really quite exciting was the idea that the T-cell engager could be highly effective even if a patient had seen prior BCMA-directed therapy. And what this means to me is that perhaps if you're progressing on a CAR T-cell, you still may have a pretty reasonable chance at a response, again, to a BCMA-directed therapy with a bispecific. The other way around may not necessarily be the same. And so I think what we learned at this meeting is that the bispecific or T-cell engagers clearly could have activity in the context of prior BCMA-exposed therapy. And I think, as a field, we need to think more about how we define what it means to be resistant to a BCMA-directed therapy. So that I think was really important and exciting and will have relevance in our daily clinical practice.

We also saw updates on a different non-BCMA-directed target. So we saw updates on GPRC5D-targeted bispecifics, also known as talquetamab. What I think was really exciting here is we saw a very high overall response rate, modest infectious complications compared to what we've seen with BCMA-directed therapy.  

Finally, what I want to wrap up with was a very small study addressing what I think is a pretty significant unmet medical need. And that was a trial from Dr. Nooka at my institution, where we evaluated a combination of carfilzomib with pomalidomide and dexamethasone, or KPD. And we used that specifically as maintenance in the high-risk group. And what we learned from that evaluation is that it appears for patients with high-risk disease that KPD maintenance is better than either carfilzomib and len [lenalidomide] or even bortezomib and lenalidomide, which historically has been what we're using.

But there remains an unmet medical need patient population, particularly the double-hit patient population, that even with KPD still didn't have a great outcome overall. So more work for us to do down the road. But certainly, food for thought for many of those other patients that perhaps don't fit into that double-hit classic category. So I think what I've given you is a nice sort of overview of many of the exciting data that were presented at ASCO 2023. Again, go to the website to see additional ones. And thank you again for listening to this brief summary of research in myeloma updates from the 2023 ASCO Annual Meeting.

ASCO: Thank you, Dr. Lonial.

Finally, Dr. Cristina Rodriguez discusses new research in treating head and neck cancer. Dr. Rodriguez is a medical oncologist at Seattle Cancer Care Alliance, an Associate Professor in the Division of Medical Oncology at the University of Washington, and an Associate Member for solid tumor clinical research at the Fred Hutchinson Cancer Research Center. She is also the 2023 Cancer.Net Associate Editor for Head and Neck Cancers.

You can view Dr. Rodriguez’s disclosures at Cancer.Net.

Dr. Rodriguez: Hello, my name is Cristina Rodriguez, and today I'm going to discuss some new research focusing on head and neck cancer that was presented at our annual ASCO 2023 meeting. As part of my disclosures, my institution receives research funding from CGEN. My takeaway from this meeting was there were a few major themes represented by the research. One of them was research on uncommon cancer types, such as nasopharyngeal cancer and salivary gland cancer. The other major theme and what was exciting for me was research on groups that were typically not represented in clinical trials in head and neck cancer. These include elderly or frail patients with many other comorbid illnesses that might have excluded them from clinical trials. Another theme was research in areas outside the developed world. In other words, resource-restricted countries. There was some exciting research coming out of that. And finally, a few new agents, novel agents that looked to have activity in patients with head and neck cancer that are going to be studied further.

So with that, I'm going to start with talking about research that came out of France, presented by Dr. Fayette. This was a clinical trial that focused primarily on the frail elderly population. A group that might make very difficult for one to enter clinical trial because of many different illnesses or not being fit enough. And this group, out of France, looked at a combination of immunotherapy and a gentler lower dose chemotherapy called carboplatin and paclitaxel. Interestingly, in this group, there was very encouraging results, including 71% of patients having an objective response or a reduction in the size of their tumor, and very few patients, less than 5% of patients, having toxicity that required permanent discontinuation of the drug. So I thought this study was particularly interesting and gives us physicians and patients who are in this situation some more options to use when we're in the treatment of head and neck cancer.

The next study that I thought was particularly interesting came out of India and was presented by Dr. Kothari. The special thing about this study was that it asked the question of the efficacy of a very low-cost combination for patients with recurrent or metastatic head and neck cancer. It's a combination that we don't tend to use here in the United States, one that involves methotrexate, celecoxib, and erlotinib. This particular clinical trial was carried out in several sites in India, and it randomized patients to this low-cost oral regimen versus physician's choice.

In other words, any type of treatment that might involve immunotherapy or antibody therapy. The main issue here being that sometimes many of these therapies are not easily accessible to patients in low-resourced situations. The investigators observed an overall survival advantage, what that means is more patients lived longer when they use the low-cost oral regimen, which was much more practical, much easier for patients to take, and had more success in improving and prolonging the lives of patients. So I thought that that was a particularly important observation. And we forget a lot of times when we're practicing in the United States that a lot of our practice patterns here may not be applicable to low-resource settings. And I think it's very exciting that research is being carried out to answer questions that are relevant to this area.

The third abstract that I thought was particularly intriguing was one presented by Dr. Glenn Hanna from Dana-Farber. And it looked at a new drug called BCA101. BCA101 is an antibody that has 2 functions. It inhibits EGFR, or epidermal growth factor receptor, very commonly overexpressed in head and neck squamous cell carcinomas. And it has a dual function, which is it modulates TGFβ, which is an immunosuppressive cytokine within tumor cells. This drug was combined with pembrolizumab in this small study and offered to patients who have never received treatment for recurrent or metastatic head and neck cancer. There was a lot of enthusiasm for this drug because in the 33 patients enrolled in the trial, 48% of them had an objective response, meaning a reduction in the size of their tumor. Anemia was one of the more common side effects that were noted. But the efficacy of this agent in this population, these patients expressed PD-L1 or had a CPS score of 1, was enough to support further study of this drug and a larger clinical trial is going to be carried out looking to see if this drug will have similar efficacy or better efficacy in a larger population.

Finally, the last abstract is one that was presented by Dr. Swiecicki. And it was an interesting abstract to me because it examined the activity of another novel agent not FDA-approved for head and neck cancer, called enfortumab vedotin. This is a class of drugs that belong to a group called antibody-drug conjugates. This is an antibody that's directed toward the target called Nectin-4 and has a small chemotherapy payload that's attached to the antibody. Unlike Dr. Hanna's study, this study was a small phase 2 trial that focused on patients who've previously been treated in the recurrent or metastatic setting and are now receiving this drug either as their second or third option after they developed recurrent or metastatic disease. 46 patients were enrolled in this trial, and 24% of patients had an objective response or reduction in the size of this tumor. Although that number doesn't seem very high, it is an encouraging signal because in patients who previously received treatment for head and neck cancer, we tend to see very poor response rates. So this is encouraging given the population that was studied. Another 32% of these patients had what's called stable disease or no significant change in the size of their tumor. So that too is quite encouraging. This drug is going to also move on for further study in head and neck cancer.

So I thought that these themes really brought about a lot of excitement for me for the future of treatments in patients with head and neck cancer, not only in developed countries but also in resource-restricted environments. And I look forward to next year and more work being done in these areas. And I'd like to thank you for listening to this brief summary of developments and head and neck cancer presented in the 2023 ASCO Annual Meeting.

ASCO: Thank you, Dr. Rodriguez.

You can find more research from recent scientific meetings at www.cancer.net.

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ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today, we're going to be discussing how parents can talk with their children about a metastatic cancer diagnosis and their prognosis. The information discussed in this podcast is based on a study published in JCO Oncology Practice titled, “Talking with Children About Prognosis: The Decisions and Experiences of Mothers with Metastatic Cancer.” Our guests today are Dr. Eliza Park and Dr. Paula Rauch. Dr. Park served as the lead author on the study, and Dr. Rauch served as a co-author on the study. Dr. Park is the deputy director for the UNC Lineberger Comprehensive Cancer Support Program at the University of North Carolina at Chapel Hill in Chapel Hill, North Carolina. Thanks for joining us today, Dr. Park.

Dr. Eliza Park: Thank you for having me.

Brielle Gregory Collins: Dr. Rauch is the director of the Marjorie E. Korff Parenting At a Challenging Time, or PACT, program at Massachusetts General Hospital in Boston, Massachusetts. She is also a member of the Cancer.Net Psychosocial Oncology Advisory Panel. Thanks for joining us today, Dr. Rauch.

Dr. Paula Rauch: My pleasure.

Brielle Gregory Collins: Before we begin, we should mention that Dr. Rauch and Dr. Park do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now, to begin, Dr. Rauch, what are some of the challenges or fears parents with metastatic cancer have in talking with their children about their illness?

Dr. Rauch: I think as parents themselves are adjusting to their own diagnosis, whether it's the parent who is living with the cancer or their co-parent, they are hoping to not burden their children, to not worry them too much, and at the same time, they want to be sure to include their children in this very important event that's happening in the life of the family, and that is a tough balance for any parent.

Brielle Gregory Collins: And I recognize that these conversations might be different for parents who don't have metastatic cancer. So what ways are these discussions different when parents have non-metastatic cancer?

Dr. Rauch: I think for me, the easiest way to talk about this is to think about how we encourage parents to talk with their children about cancer, and that varies depending on the age of the child. But 1 way that we often talk with parents that they may explain cancer to younger children is to talk about the fact that our bodies are made up of millions and millions and millions of teeny-weeny, little cells that are kind of like Legos, and that what cancer cells are, they're kind of like Legos that are mixed up and don't fit together right and can't do their jobs right. When someone has an early-stage cancer, the goal of treatment by their medical team is to be able to get rid of the cancer completely. The goal of treatment when someone has metastatic disease, when those mixed-up cells are in more than 1 place in someone's body and the treatment can't make them go away completely, the goal is to keep those mixed-up cancer cells as small as possible and in as few places as possible so they don't interfere with a person's healthy cells.

Brielle Gregory Collins: Okay, thank you for explaining that. And what do parents with metastatic cancer need to know before talking with their children about their illness?

Dr. Rauch: I think parents generally know their children well. And so part of what they are thinking about is, first off, what is communication like typically in their household, what's the developmental stage of their child, what's their child's understanding of things, and also importantly, what their child's temperament is. You could think about temperament in children as being a little bit like personality in adults, but temperament is a way of capturing that kids have a typical way of adjusting to or understanding changes in their lives and in events that happen at home. And so taking all those things into consideration, parents may want to share information at a particular time, maybe at the beginning of a weekend when they have time to process with their child. They may have a good sense of what their child's understanding is. An older child may know a lot about cancer, a younger child, almost nothing. So we really think about parents as the expert on their own children. We have a lot of experience with the kinds of words that you can use in talking to children, but it's always a partnership of parents knowing their children and what their usual way of communicating is and then adapting this particular set of information to that knowledge base.

Brielle Gregory Collins: Okay. And I want to talk a little bit about prognosis and what parents should know about talking with their children about their prognosis. So first of all, just getting into that topic, why is it important for parents with cancer to know what their prognosis is?

Dr. Rauch: Well, you can't really explain anything to your child that you don't understand well yourself. Many parents will tell us that they find themselves asking really important questions of their oncology team because their children ask them really good questions or because even if they're not quite ready to describe fully something to their child, it's kind of like they want a script in their back pocket that they can draw upon if questions come up. When we have a sense of how we want to answer something, then it's easier to present a calm presence to children and really then to help them to feel their questions really are welcome.

Brielle Gregory Collins: Thank you, Dr. Rauch. And Dr. Park, branching into the study, you've described several different approaches that parents can use when talking about their prognosis with their children. So can you summarize for us what those strategies are?

Dr. Park: So that's a good question, and I would say, in taking a step back, kind of the overarching kind of goal of the study is that we know that these conversations can be nuanced and that they can be challenging. So given that we know that there's multiple decisions and challenges related to this, kind of how are the ways that parents who are remarkably resilient, thoughtful, find ways to kind of thread this needle in a way that makes sense for them and their families? And I think 1 of the main takeaways is to think about it is almost as, "What does honesty mean kind of when talking about cancer?" Because what can be an honest conversation in 1 family can look dramatically different from another's, and that's not to say that either way is better or worse, just different. So for some families, that meant discussing details about what their scans looked like and what that meant for their treatment and for the stage of their cancer, and for other people, it meant bringing up the possibility that their illness was chronic or may not be curable. And what we found is that for most parents, it was less about whether they should say something at all but rather a timing of when, and that takes a variety of decisions related to the factors that Dr. Rauch mentioned earlier.

Brielle Gregory Collins: I know in the study, there were several strategies that were outlined, so I want to go back to that for a minute. Do you mind just walking through what each of those strategies individually was and what they mean for parents who might be talking about this with their children?

Dr. Park: Absolutely. So as I mentioned before, there was many different strategies. So what I'm going to describe may not reflect everyone's experience, but the main 1 that we identified is parents simply wanted to be honest, and what that meant in terms of discussing their prognosis then took a variety of different forms. And so the strategies that came up most frequently that parents described using was, 1, kind of introducing the language of illness that might not get better in a way that can be fairly gentle. And so the language that many parents used was kind of, "Treatment for the rest of my life," and this was a way of signaling some of the changes that are going to be happening in their family moving forward but not necessarily including other statements that the children may not necessarily-- or the parents may not necessarily be ready to discuss right then and there.

The other common strategy that parents, I think, very instinctively used was having these many conversations over time. I think that the truth is this is not a 1 and done, to use a basketball analogy, conversation. This is something that happens kind of over the dinner table, at bedtime, in car rides, over the course of weeks, months, or most commonly, years, and there are a lot of children who grow up with a parent with cancer, and over time, the details can kind of emerge.

The third major way that parents would often approach these conversations was via questions, and the truth is that these conversations about prognosis were not always initiated by the parent. We had children as young as 4 who were asking questions about kind of what this means and what might happen next. And so parents often kind of look to their children's questions as kind of cues for cues of what they believe their child may be ready for in terms of specifics.

And I would say that the kind of last strategy is something that is just instinctual that I think every parent does without even thinking about it, which is just really reinforcing their love and their desire to help reassure their children that this may be information or news that is not desired but that they want the best for their children and to help their children feel secure, and I think that was probably the message that emerged in almost every description of parents' conversations with their children.

Brielle Gregory Collins: Thank you. And in the study, the most common barrier to having these discussions was that the parent didn't know what to expect in the future. So can you tell us a little bit more about that?

Dr. Park: Yes. So this was something that I think can be overlooked when we think about just, "What are the challenges in having these conversations?" I think we all understand that it can be emotionally taxing for parent or child, depending on what is happening with the illness, but this uncertainty about what happens in the future, I think, is a reflection of just how much progress has occurred in cancer therapies over the past decade. Many of our participants in the study had breast cancer, and these days, women can live with metastatic breast cancer for a decade or longer, and other individuals may not have quite the same expectation. And so because it can be so hard for patients as well as their providers to kind of be able to predict what happens next, it can be really challenging to figure out, "What does my child need to know next or even right now?"

Brielle Gregory Collins: Thank you for outlining all that. That's very helpful. And Dr. Rauch, is there anything that all parents should do when having these conversations about their prognosis with their children?

Dr. Rauch: I think most parents may not even think about this quite as prognosis but really more about what is going on with them. Just like any other family event, there is an illness that is underway within the parent, but there are also all kinds of changes in their home and things that will directly affect the child. So first, I think it's important to name the cancer because if you name it, then it can be talked about. If it's left as a euphemism, a bump, a lump, a boo-boo, that can be confusing. So I think the very beginning, even for children as young as 3, is to name it so it becomes something that is - I use a made-up word myself - talkaboutable so that there's the possibility and really the welcoming of questions in conversation. So I would say that's the first part.

And then, I think, a combination of what the goals are of treatment for the parent and also, what the impact is day to day, week to week, month to month for the child. And the amount of time that a child is thinking, and maybe it is really moment to moment for a preschooler, it may be a much longer amount of time for an older child. So thinking in terms of those bits of time that makes sense at different ages and then, I think, recognizing that children who are even 7 years old and older are not just getting their information from their parents, but they're getting information from lots of other places. Kids of all ages may overhear information at home, and that's the most confusing way to get clear information about cancer and about how the cancer is unfolding for the parent. So continuing to check in with kids, "What have you heard? What are you wondering about?" And certainly, for older kids, addressing the challenges of children getting information from the internet as opposed to directly from a parent.

Brielle Gregory Collins: Got it. So you definitely don't want it to be this elephant in the room. You want it to be an open discussion, and you want to be available to address the questions that your child might have and, of course, mitigate any fears that they might come across when they go on Google or talk with other people, things like that.

Dr. Rauch: Yeah, you want to give the message, "Don't worry alone." And I'll sometimes say to parents of adolescents, "Let your teenager know that you're going to either worry about them or worry with them." And if the teenager shares their concerns of what they're hearing, then the parent and the teenager can problem-solve together. If the child or teen doesn't share their information, then the parent's going to worry about them, and when a parent worries about instead of with their teenager, the parent is much more likely to be off the mark and frankly, more annoying to teenagers, and many teenagers will respond with a smile to that, "Oh, yeah. If you're guessing what's on my mind, you're going to annoy me more. If we can talk about it together, we can actually address the things that are front and center." And I think helping teenagers to recognize that what they read about on the web is about a large group of people and it's about the past. So it's neither about how things are going to be for the individual, their parent, nor is it representative of the future of cancer care. So the best guess about a parent's illness trajectory is going to come from talking with the parent and the parent talking with their medical team, and that's an important message to deliver to kids really in older elementary school age, middle school, and adolescents.

Brielle Gregory Collins: Definitely. That's helpful to know. And for parents who might be struggling with a child who doesn't want to talk about the illness, what advice do you have for people in that position if their children don't want to talk about it?

Dr. Rauch: So I think parents need to give updates to their child and say, "I want to be sure that you have the opportunity to hear, and I want you to hear from me. You might overhear me talking to your aunt about this or your grandparent or about that. So here's what's going on.” Because, again, overhearing information is the worst way to have it communicated. It's not respectful to the child either to feel like, "Oh, my parent is talking to other people about the specifics of their illness and leaving me out." So communicating to a child, "I don't want you to worry alone. Here's what you might hear me talking about with others. Here's how my treatment or my illness may affect us at home and you, the child, in particular. I am eager to hear your questions, but it's up to you to let me know what's on your mind." And then I think for some kids, it's also giving them permission to talk to other caring adults, who are also a good source of information. Some kids can't bear to have the conversation with their parent because it's upsetting. They can see that their parent is upset or they feel upset themselves. But they might talk to their best friend's mom, or they might talk to another family member, or they might talk to a co-parent. And guiding children and teenagers to good resources, and by resources, I mean people who they can discuss the parent's cancer with, is also important.

Dr. Park: I would also add to that, as a clinician, I often ask patients, "What is helpful for you to know?" And what I might assume is helpful for them to know may be completely different than what is the truth, and we often find that that can be another way to help kind of open up some conversations to find out what are the kind of lingering questions or kind of unknowns in their child's mind.

Dr. Rauch: I also find that some teenagers who are not so eager to talk, if you ask them, "What's the dumbest thing anybody has said to you?", that sometimes is a gateway to a conversation.

Brielle Gregory Collins: That's a great question. And Dr. Park, going back to the study, many parents in the study were worried about upsetting their children by talking about their prognosis. So what can parents do to help if they're in this situation?

Dr. Park: Well, I think the truth is that parents are worried about upsetting their children because these conversations are hard for a good reason, and there is a need for balance and for weighing these different considerations. I think we find that parents can do things like kind of put their toe in the water. I don't think all this information needs to come out on the very first time they're telling their child about their diagnosis. If anything, we find that most parents take a more gradual approach. One of the things I often think about is that it takes time for adults to adjust to a cancer diagnosis and what that means. And similarly, it takes time for kids, too, and so there isn't necessarily a rush to kind of put it all out there on the very first conversation.

And the other things that I think that are helpful can be the more clear an individual is about kind of what they can expect with their illness and the different possibilities, I think, can at least reduce some of the uncertainty on the parent's end. It may not necessarily make the conversation less worrisome for the parent or the child in terms of that immediate moment, but I think oftentimes, parents can often then give additional information that they may not have known if they hadn't had more information from their provider about what the next treatment might be, if this 1 doesn't work the way we would like it to, or that things may not necessarily happen, things may not suddenly change on the drop of a dime tomorrow. I think that sometimes there can be uncertainty on the parent's end, and that is something that is very modifiable with having some conversations with their health care team.

Dr. Rauch: I think often parents can reassure their child that they're not expecting anything to happen this week or next week or this month or next month or today or tomorrow and that if things change, that they will update their child. And then the other thing I would just say is that parents are often very, very worried that when they share information with their child, their child will be so upset and sort of almost like that their childhood will stop at that moment. And in my experience, the vast majority of parents are surprised that their child accommodates as quickly as he or she does. It doesn't mean that it's not upsetting. It is upsetting, and actually, we would be worried if a child or a teenager wasn't upset by a parent's life-shortening cancer diagnosis. It is upsetting.

So using as the yardstick whether children are transiently or for a time upset is kind of the wrong yardstick. We would expect just lots of things upset kids, then they accommodate, and the parent is there to help them through that process. If parents wait too long to begin the conversation with their child, then they really have deprived their child or teenager of the opportunity to co-process this difficult news. Think about it like an elevator if you're starting at the penthouse, and you're going down a floor at a time. It's a lot easier to adjust to a gradual stepwise change than it is to go from the penthouse to the basement in free fall. So slowly having multiple conversations, as Dr. Park was discussing, but also not being afraid to let children be upset. Most parents have experienced their child's distress about a host of things. I've been watching my toddler grandchild start in daycare. He weeps when he starts in the morning, and then he's fine at the end of the day. I don't mean to minimize how different this challenge is, but part of what we do as parents and grandparents is to provide children with the opportunity to be safely upset with us.

Brielle Gregory Collins: Right. And I want to go back to this idea of the questions that children ask. I know we talked about the importance of addressing those questions. And Dr. Park, in the study, parents often relied on their children's questions to help guide these conversations, but are there any questions that parents should be asking their children when it comes to their illness?

Dr. Park: I think the truth is that we would like for parents to be listening even more than telling, and by that I mean that the main concern of parents, as Dr. Rauch mentioned earlier, is whether this is going to be too upsetting for their children, and that is not something that you can necessarily know or predict about how your child is kind of coping with this news by a single conversation or by you talking to them. Rather, I think it means kind of finding out kind of, "How does this impact their child's lives? What are the questions that they have been wondering about?" And really just, I think, being curious about how their child is thinking about this and what they understand, I would say, would be the kind of questions we would encourage all parents to think about. The other thing I also like to say is that children are remarkably curious people. I have young kids, and I think our dinner table conversations are essentially 1 long 20 questions pretty much every night, but not every child is necessarily going to feel comfortable asking some of these questions. And so having the parents at least find out what their children want to know, I think, can help put some of that expectation or pressure to ask these kind of bigger questions off their kids and perhaps kind of in the parent's hands.

Dr. Rauch: I have a couple of questions that I might suggest for parents of different ages. So I think parents of young children, whether it's the parent or a co-parent or someone else that asks to find out how young children understand why someone got cancer, it happens that sometimes in this early age where kids really feel like they caused the things that happen around them, they may have a misconception that they caused the parent's cancer or that when the parent is fatigued, that the fatigue is because the parent doesn't like them or is bored with them or irritable at them. So I think remembering that very young children are particularly self-centered, and that's developmentally normal to ask questions there. I think sometimes for older kids, just asking what someone who hasn't lived with a parent with cancer-- what other kids don't get about what it's like to be them can sometimes again be a way into having a child share what they feel isn't well understood by their peers or isn't well understood by the people around them.

Brielle Gregory Collins: Thank you for breaking those down. And thank you both so much for your time and for sharing your expertise today. It was so great having you.

Dr. Rauch: Thank you.

Dr. Park: Thank you.

Brielle Gregory Collins: For more information on this topic, please visit www.cancer.net/talkingwithchildren.

ASCO: If this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Michael Williams will discuss some of the new research in lymphoma that was presented at the 2018 American Society of Hematology Annual Meeting, held December first through fourth in San Diego, California. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center, and Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine.

ASCO would like to thank Dr. Williams for discussing this topic.

Dr. Williams: Hello. This is Michael Williams. I'm a professor at the University of Virginia Health System in Charlottesville, Virginia, and I'm reporting today on some exciting advances in lymphoma that were presented at the Annual Meeting of the American Society of Hematology, which was held in San Diego, California in early December 2018. Well, there were a number of areas of lymphoma that had important reports, and I'm going to just give you a small sampling of these today.

We'll start with a new treatment option for patients with follicular lymphoma. Traditionally, this type of lymphoma, when it's symptomatic and needs therapy, the treatment of choice has been chemotherapy combined with a monoclonal antibody such as rituximab or obinutuzumab. But investigators, in a multicentered trial, decided to test whether you could use a chemotherapy-free treatment approach for patients like this by using rituximab combined with lenalidomide, which is also known as Revlimid, as a substitute for chemotherapy. And this is based on the fact that Revlimid plus rituximab has synergistic activity in patients with relapsed disease, so maybe we could see acceptable, high responses when it would be compared directly with rituximab plus chemotherapy.

So the way the trial worked is this. Patients who needed therapy, who had advanced-stage follicular lymphoma—they had never had any therapy before—were randomized to either the rituximab-lenalidomide combination or a rituximab-chemotherapy combination that could include the regimens CVP or cyclophosphamide, vincristine, prednisone, the same combination given with daunorubicin, or the CHOP regimen, or rituximab combined with bendamustine.

So over 1,000 patients were treated in this multinational study and the goal of the treatment, of the study was to prove that, actually, the ritux-lenalidomide was superior to the chemotherapy regimens. So the results showed, not superiority, but comparability. The complete remission rate between rituximab-len and ritux-chemotherapy were really identical, 48 and 53 percent, and the 3-year likelihood that the patients were progression-free, so had had no recurrence of their disease, was identical as well: 77 to 78 percent. There was no difference in survival which was 94% at 3 years in both arms.

The toxicities differed, however. There was more rash with the lenalidomide combination, whereas low blood counts and the need for growth factor support such as G-CSF was greater with chemotherapy. And it was also interesting that some of the traditional risk factors didn't seem to apply, as much, for lenalidomide. So what would be considered higher risk patients treated with chemotherapy, seemed to do somewhat better with the lenalidomide combination. The importance for a patient with untreated follicular lymphoma who needs therapy is that a chemotherapy-free approach with rituximab plus lenalidomide can be considered equivalent to rituximab-chemotherapy. It’s worth discussing this with your oncologist when you're considering what treatment to use initially.

The next subtype of lymphoma that I want to discuss is diffuse large B-cell lymphoma, and there's 2 presentations that I'm going to summarize. One, in patients with advanced stage disease, meaning stage III or IV. This identifies patients who have disease both above and below the diaphragm, to make it stage III, or stage IV means they've got bone marrow or other sites of involvement such as liver or bone. And the question being asked in this trial, which was part of the International GOYA trial, will take just a moment to explain. So the original GOYA trial compared whether a newer form of anti-CD20 monoclonal, namely obinutuzumab, which is also called Gazyva, how that would compare with the standard established monoclonal antibody, rituximab. And the initial findings of this study found that there was no benefit for the newer antibodies. So rituximab and CHOP chemotherapy was equivalent to obinutuzumab and CHOP chemotherapy in overall outcomes.

But there was an opportunity with this trial to answer a question that's been out there for many years, and that is how many cycles of treatment does one need? So the investigators took advantage of this large study which included 712 patients who were randomized to rituximab plus CHOP. Just over 500 of them received 6 cycles, and the remaining 186 received 8 cycles. Even the patients who got 6 cycles of CHOP chemotherapy also got an additional 2 doses of rituximab, so the immunotherapy monoclonal antibody was equivalent between the 2 arms. And the results of this showed that there was really no difference at all with a followup of about 3 years. Response rates were equivalent and there was no difference in the patients staying in remission. It didn't matter in terms of survival which was excellent in both arms. There was, however, more toxicity in patients who received 8 cycles, including cardiac problems, infections, etc.

These results showed that, I think we can finally put to rest the use of 8 cycles of rituximab-CHOP chemotherapy for advanced-stage large cell lymphoma. It's been an unknown entity because we never had a direct comparison of these. So we can now say that 6 cycles plus the additional 2 doses of rituximab is a standard for advanced-stage diffuse large B-cell lymphoma.

Now, what about patients who have limited-stage, so stage I or II diffuse large cell lymphoma? That means just a single lymph node area's involved or 2 adjacent lymph node areas. In the past, these were treated either with 6 cycles of rituximab-CHOP or sometimes cycles of R-CHOP plus local radiation therapy. And in this study, which took a long time to complete; it began in 2005, but it enrolled 592 patients who were then randomized to either 4 cycles or 6 cycles of treatment. Radiation therapy was not planned for any of these patients except for very specific locations of involvement such as testicular DLBCL where radiation therapy is a standard.

So the take-home message after over 5 years of follow-up for patients on this study showed that 4 versus 6 were identical. So 89% of patients were still in remission at 3 years after completing treatment, and the overall survival was really impressive, 98 to 99 percent in the 2 arms. So there was no benefit with limited-stage favorable disease. Now, who are these patients? So younger than age 60, stage I or II disease, and normal LDH. They did not have bulky disease, meaning there was no nodal mass more than 7 and a half centimeters. So if you fit those criteria, then you can benefit from a de-escalation of treatment and be spared the additional 2 cycles of R-CHOP.

Now, sticking with the topic of diffuse large B-cell lymphoma, a challenging problem in our field is for patients who relapse after their initial therapy, or in some cases, fail to respond to a treatment like rituximab-CHOP or an equivalent immuno-chemotherapy regimen. And a very exciting advance in the field, over the past few years, has been the development of chimeric antigen receptor T cells or CAR Ts. Traditionally, what we've done with patients who relapse or have resistant diffuse large cell lymphoma is to give them a second-line, high-dose chemotherapy regimen, and if they showed a good response to that, they could then go to a dose-intensive treatment with a follow-up consolidation by autologous stem cell transplantation. And with that, you can cure, overall, about 40% or so of patients. The CAR T-cell approach takes a very novel immunotherapy effort, and that is that a patient's own T-cells are removed from the peripheral blood, and then in the laboratory, they're modified and reprogrammed so they can attack the patient’s diffuse large B-cell lymphoma cells that are resistant to chemotherapy.

So there were 2 important follow-up studies, each of them involved 1 of the agents, the CAR T-cell products, that are approved by the Food and Drug Administration for patients with relapsed or refractory diffuse large cell lymphoma. The first used the CAR T known as axicabtagene ciloleucel. It's quite a complex name, but it goes by the abbreviation of axi-cel or the trade name is Yescarta. So in this study, the investigators wanted to show that this is a treatment that can be extended to many centers with the product, the CAR T being made in a central facility by the pharmaceutical company. So it was a retrospective study of 295 patients at 17 international centers: a lot of patients across a broad spectrum of sites in North America and Europe.

Virtually all the patients were able to develop and obtain a CAR T product. It included patients with some of the higher risk forms of the DLBCL such as double and triple-hit lymphoma. About 3% of patients died during the treatment, although only 1% of these were felt to be related to the treatment itself. The response rates were quite good, with about 80% of people responding. The complete remission rates at 30 days after the CAR T infusion were 47%. So it proved that you can use this centrally manufactured product. So the patients T-cells are collected at the local center, they're shipped to the manufacturing facility, the CAR Ts are generated, sent back to the home institution, and then infused. And I'll say a word in a moment, after I introduce the next paper, to explain some of the side effects of this treatment.

So the second study was also presented at the ASH meeting and published simultaneously in the New England Journal of Medicine in early December 2018. So this used the second FDA approved CAR T known as tisagenlecleucel or Kymriah. In this study, there were 93 patients who were able to receive a CAR T-cell infusion, 40% of them achieved a complete remission, and another 12% had a partial response. And that a year after their documented response, two-thirds of these patients were maintaining the response, including 79% of those who achieved a complete remission. So this trial again confirmed across multiple centers that CAR T-cells can be an effective therapy.

The side effects of both of these drugs can include something called cytokine release syndrome where the immunologic effects, essentially, release cytokines into the blood that can mediate a capillary leak, respiratory troubles, and low blood pressures, that can, in some cases, require intensive care unit support. This can be managed by other mediators that tamp down the cytokine effect such as an interleukin-6 antagonist.

The other toxicity which is less well understood and problematic can be neurologic effects which can include confusion, speech alterations and even coma. But again, approaches and treatments to identify and manage this are being developed. So CAR Ts have become established. They're available at a number of centers, but it's important to consider this as a treatment option in the setting of relapsed or refractory diffuse large cell lymphoma. The long-term curability is still unknown, although it's encouraging that patients with very resistant disease who'd get a good response can maintain that response out to a year and more. So we're going to be very interested to see how the longer-term follow-up comes together.

The final topic I wanted to mention today is Waldenstrom macroglobulinemia. So this is a unique form of indolent B-cell lymphoma where the lymphoma cells release a monoclonal immunoglobulin into the blood known as IGM. Now, IGM is a very large antibody, and because of that, when the levels are very high, patients can have problems with high viscosity or thickening of the blood, which can cause confusion, vision changes, sometimes respiratory problems. And these patients also can become anemic or develop enlarged lymph nodes or enlarged spleen. So one of the standard treatments for this disease is, again, the immunotherapy monoclonal antibody rituximab, but the responses are typically incomplete and somewhat short-lived. So it was exciting, a couple of years ago, when the targeted tyrosine kinase inhibitor, ibrutinib, which targets the bruton tyrosine kinase in malignant B-cells. This is an agent that's approved in chronic lymphocytic leukemia, and certain lymphomas such as mantle cell, marginal zone, as well as lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia.

So here's the study. Investigators had shown that if you combine rituximab with ibrutinib, that the response rates were improved as compared with rituximab by itself. And in a follow-up study that looked at this over a longer period of time, these benefits of the combined therapy were confirmed. These included patients without prior treatment or with prior treatment, with either chemotherapy or rituximab. And there was a confirmed benefit for the ibrutinib-rituximab combination in patients, whether they had had treatment before or not, and regardless of certain genetic markers that we use to assess risk in Waldenstrom. It was also shown that because these treatments continue indefinitely, as long as patients are responding and tolerating therapy, that the response rates improved over time. The side effects of treatment with ibrutinib are well-known, now, after several years of use across a variety of diseases, as mentioned, and include diarrhea, sometimes rash. You can see problems with easy bruising or bleeding, atrial fibrillation, and sometimes skin rash, or muscle and joint aches. But most patients are able to continue therapy and to benefit from it over an extended period of time.

So the combination of ibrutinib plus rituximab was shown to add benefit compared with rituximab alone, and again, is a treatment approach and option that you could consider whether you have previously untreated or relapsed Waldenstrom macroglobulinemia.

So overall, it was a very exciting meeting. We've had practice-changing data presented, and I've given you just a sampling of those. I think it's important for anyone dealing with lymphoma, or related malignancy, such as CLL or multiple myeloma to be very encouraged by the progress in the field, the opportunity to get much better responses with less toxicity and with minimal or no use of traditional chemotherapy. So we're pleased to be able to offer these treatment approaches for our patients. And I thank you for your taking part in the podcast and hope you found it useful. Thanks again.

ASCO: Thank you, Dr. Williams. Learn more about lymphoma at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

Cancer.Net is supported by ASCO’s Conquer Cancer Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

Treatment for head and neck cancer can often cause side effects that make it difficult to eat. In this podcast, dietitians Maureen Gardner and Annette Goldberg discuss several side effects that may be caused by head and neck cancer treatment and offer tips for managing these side effects and taking in enough nutrients, including information about feeding tubes.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Brielle Gregory Collins: Hi, everyone. I'm Brielle Gregory Collins, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today we're going to be talking about coping with the mental and emotional challenges of cancer through exercise. Our guests today are Dr. Sheila Lahijani and Sami Mansfield. Dr. Lahijani is an associate clinical professor of psychiatry and behavioral sciences at the Stanford University School of Medicine and the medical director of the Stanford Cancer Center Psychosocial Oncology Program. Dr. Lahijani is also an advisory panelist on the Cancer.Net Editorial Board. Thanks for joining us today, Dr. Lahijani.

Dr. Sheila Lahijani: It's truly my pleasure to be here today, Brielle, with all of you.

Brielle Gregory Collins: Thank you. Ms. Mansfield is the founder of Cancer Wellness for Life and the director of Oncology Wellness for the Sarah Cannon Cancer Institute at HCA Midwest Health. Thanks for joining us today, Ms. Mansfield.

Sami Mansfield: Thanks, everybody, for having me. Excited to be here as well.

Brielle Gregory Collins: Before we begin, we should mention that Dr. Lahijani and Ms. Mansfield do not have any relationships to disclose related to this podcast, but you can find their full disclosure statements on Cancer.Net. Now to start, Dr. Lahijani, how can a cancer diagnosis impact a person's mental and emotional well-being?

Dr. Sheila Lahijani: Thanks for asking this question, Brielle. Usually, when people want to know the answer to this, what I preface it by saying is that there is a spectrum of responses. Many people find themselves to be quite distressed because cancer continues to have quite a lot of stigma, both in this country and as well as internationally. People oftentimes associate it with feelings of despair, anxiety, and helplessness. Having said that, many of these responses and reactions are normal. Some people can progress to have many more significant emotional responses and reactions that can become more disruptive to their lives and to the roles that they play a part in. We really try to meet patients where they're at to better understand how they've previously coped with past life challenges and/or traumas and to identify what strengths they have, what coping mechanisms they have to help them manage the distress associated with cancer. There are patients who also have a history of past psychiatric diagnoses and problems, in which case getting diagnosed with cancer and undergoing cancer treatment can cause a lot more difficulty. So each person is different. There are a lot of, quote-unquote, "normal" reactions, responses and reactions, that we as providers do validate and reflect back to the patients. And then there are those that can cause many more problems, and those are the ones we really need to address.

Brielle Gregory Collins: Okay. And getting into some of those problems, what are some of the most common mental and emotional challenges that people face during cancer?

Dr. Sheila Lahijani: The majority of people feel very anxious. And I've shared this with others and share this with my patients: being anxious means something. It means that you care about something. You care about yourself. You care about your life. You care about people in your life. And so it's a sign. It's something that needs to be tended to. People suffer from mood symptoms such as depression as well, difficulty coping, feelings of loss and despair. Those are the most common reactions. Some people can develop other difficulties related to side effects of cancer treatments as well. And also, there are people, as I mentioned, who previously have suffered from psychiatric symptoms, where things can become much more difficult and challenging, affecting their way of thinking: problems with cognition, memory, recall, things like that. So to summarize, largely mood disturbances and mood symptoms in the forms of anxiety and depression. Panic is also a part of that, as well as post-traumatic stress. And there are others who have previous symptoms that can become more problematic. So we really try to evaluate both mood and thinking in our patient population.

Brielle Gregory Collins: Thank you so much for walking through those. And I want to talk a little bit now about exercise and how that can play a role in coping with some of these challenges. Ms. Mansfield, what is considered exercise, and what are some of the benefits of exercising during cancer?

Sami Mansfield: Great question because there are so many different terminologies around exercise and physical activity and fitness. So I think we should start there. The terminology of physical activity is probably the most broad thing that we talk about. Physical activity is anything that we do to move the body, anything from rolling over in bed, getting up, brushing your teeth, etc. Exercise is a physical activity that is more defined or maybe has a purpose. And so it might be a goal to get stronger or a goal of rehab or prehab in this particular patient population. Or some people just want to be able to walk a 5k or run a 5k. So exercise is more intentional. And that's really how we try to define it in the literature.

From a cancer patient perspective, probably the most broadly impactful side effect management tool for exercise is actually fatigue because that is where we have a depth of evidence both in physical activity and inactivity differences. And related to fatigue from the mental health side, we see a strong benefit of both exercise and physical activity in anxiety, depression, stress management, sleep quality. So I think it's important for our audience to know that anything that you do for movement is good. Having a planned and structured movement program known as exercise is going to be ideal because the bottom line is we want you to reach your goal the quickest and without kind of feeling like you're not getting a lot of benefit to movement. And so that's why exercise really does have a significant role and why I think a lot of people really strive for, "What should I do? What does that specific exercise plan look like?"

Brielle Gregory Collins: Got it. And I want to circle back to some of the challenges, Dr. Lahijani, that you outlined earlier. So how does exercise help address some of these challenges of cancer specifically?

Dr. Sheila Lahijani: Well, I love this question. And I'm very informed by what my colleague, Ms. Mansfield, just described. Exercise and physical activity, in my opinion, are so beneficial to patients who are already diagnosed with cancer, as well as those patients who may be at risk for developing cancer-- any of us, really, to reduce our risk for certain kinds of cancer. There have been many studies that have been done that have demonstrated that intentional physical activity, as my colleague termed it, in the form of exercise can ramp up certain biological processes that contribute to improvements in cognition as well as memory function. There's a factor called a “brain-derived neurotrophic factor” which can get increased with physical activity and exercise. At the very molecular level, muscle cells can play a part in reducing the progression of disease and even potentially metastases. So there's a lot to be said biologically. As well as psychologically, it really can offer quite a lot of benefit to help people manage their distress through focusing on momentary breathing, momentary muscle relaxation. And there is also a social component to it. Even if someone is participating in an activity like this by himself, herself, or themself, there is something to be said about the communal experience of being up on your feet, moving yourself, and not being so isolated and alone, which is very much a problem for patients who undergo cancer care.

Brielle Gregory Collins: That's a really good point. And Ms. Mansfield, I want to get a little bit into the specific things that people can do. So what kinds of exercise can help people with cancer cope with these challenges?

Sami Mansfield: Now, it's a great question because that's what everybody wants. What should I do, right? And I tell everybody let's just start, number 1, with avoiding as much true sedentary behavior as possible. And I say true sedentary behavior because when you are just sitting and doing perhaps mindless activities, watching TV, there's a lot of exercises that can be done when you're seated, which is great for patients that have high amounts of fatigue or balance challenges. And I tell everyone, "Lift an arm. Lift a leg. Flex your toes and feet a couple of times, roll your shoulders, and you've just moved." It doesn't have to be vigorous or difficult. It just needs to be movement. So I think just thinking about these 1-minute, we call it “exercise snacks,” make a much more significant impact throughout the day than feeling like, "Oh, I've got to go to the gym and exercise for 30 minutes," or you might even have physical therapy. And the volume might be too high for people. So I want people to think first in small 1-minute movements.

But the next piece of this is, we've studied the different modalities of exercise between aerobic exercise, thinking about things like walking, or chair-based, like marching in the chair, swimming, biking, whatever that may be. And resistance training exercises that use muscles. You could do something with weights, soup cans. You could do bodyweight exercises that build muscle. We've studied them separately and together. And what we've learned is that for the emotional side effects, specifically anxiety, depression, having a combination of these movements is going to give you the most significant benefit. So my advice is do a minute of marching, whether that's in your chair or standing, then maybe do a chair sit-to-stand 10 times and a couple of countertop pushups, and you've now hit a full-body routine exercise regimen in under 5 minutes. I do think that people need to remember although there are recommendations of how much you should strive for, there's no reason you have to do the whole recommendation of 150 minutes of moderate activity per week to see benefit. Start with just 1 minute at a time, 1 movement at a time, and try to mix it up. Make it fun. Add music. Make it a challenge. Make it something that you feel that you can attain because you will feel better and also accomplished. And that does improve your well-being, to feel like, "I did that. I did my 1 thing a day." And that's really phenomenal and goes a long way to how people feel mentally.

Brielle Gregory Collins: Absolutely. And I love that term you use of “exercise snacks.” I think that's a really helpful way of looking at it. So for someone who's maybe just getting started with exercise, what is your advice for them as they manage their cancer diagnosis and are trying to look toward exercise as something that they want to incorporate into their lives?

Sami Mansfield: That's definitely the question I love to answer. Because if somebody's motivated, we want to get them there quickly or get them to find a resource that helps them feel successful. I kind of go back to the whole “exercise snack” piece. I think it's more important that people realize it's better to do a little something every day than to think, "Oh my gosh, I need to hit 30 minutes today, and then for the next 3 to 5 days, I don't do anything." I really advise start small, start manageable, and look for something that you can do without having to add extra barriers to your life. As an example, if getting somewhere logistically on time doesn't work for you, start with 5 minutes of things that you can do from your home. I do think there is a really important resource within most of our cancer spaces. We have oncology rehab programs. We have trained exercise professionals that can guide you. But I think people don't realize that just moving around their house, maybe 1 flight of stairs if you can do that, is a really great way to get started. There's a lot of great YouTube videos you can try. There is definitely—talk to your physicians. They might have some great ideas. But starting daily, consistency really is going to make the biggest difference than just going, "Hey, Saturday is my day to exercise." I think we can all do a little bit in that snack fashion. And I don't know. I think we can all agree snacks are good. We all like a few snacks now and again. Definitely.

And I also kind of have this thought about-- people say, "Well, if they have cancer, should they do yoga?"   And my answer is, "Well, do you like yoga?" I mean because yoga has a lot of really great resources for mental health and breath to movement and mindfulness and that grounding effect. But for someone who doesn't like yoga, which I will admit yoga is a little bit of my challenge so I push myself to do it, someone telling me to do yoga every day versus maybe exercises that I enjoy, I would be a little bit more down in the dumps about it, that you're taking away maybe what I love. So I think 1 thing, really thinking about what's the type of exercise you like to do, is it reasonable for you to continue that? If you used to run and maybe you have a lot of neuropathy in your feet, it might not be the most reasonable now. But what is the exercise that you enjoy? And that should also be part of that first thing that you do every day, not your, "Well, someone told me I should do yoga because they enjoy doing yoga," piece. And I think that's something that we need to think about in exercise. It still should be enjoyable and have good music. I think music is key as well.

Dr. Sheila Lahijani: I think it's really important to highlight as well that cancer causes so many life disruptions: disruptions to different roles, activities, functions, whatever it may be. And in speaking about intentional physical activity and exercise, it's an opportunity to create a routine and to try to lessen the impact that's caused by the disruptions.

Sami Mansfield: The pandemic certainly accelerated that for those of us who don’t even have cancer. I don't know if anybody here also experienced this.  But I remember I was working out in a gym setting-- and we actually had our own-- we ran a gym space at the time in Kansas City for cancer survivors. So we took that virtual. But I struggled with my routine. I was like, "Wait a minute." And I could go to my own gym that was private, right? But I really struggled with the mentality of like, "It wasn't my routine." And when your routine slips, you just feel very out of control. I think 1 recommendation we should make for all of our listeners, physicians, or those of us that are working in the field is I recommend starting every day with a minute of movement. I don't care if you're doing a few arm circles where you're waiting for your coffee or whatever, but there is something about getting your blood flow moving quickly that makes a really big difference. So whether that's, "Before I brush my teeth, I'm going to just do a couple of leg swings or a couple of countertop pushups or something simple every single day." Or if you're in bed, you do something in bed, even if it's just your foot flexion or drawing the alphabet where you're doing something to stimulate movement." You bring up a really good point, that we need to make that ritualization or routine, but make it also very accessible for people.

Brielle Gregory Collins: Absolutely. Thank you, Ms. Mansfield. That's really helpful. And Dr. Lahijani, in addition to exercise, what else can people with cancer do to cope with some of the mental and emotional impacts of their diagnosis?

Dr. Sheila Lahijani: Thanks for asking this question. And I want to also preface this by saying so much of what we're talking about is essentially what is now a field of exercise oncology, right? And so there's more and more literature available and resources that emphasize the benefits of exercise in this patient population and how the effects of other treatment modalities, such as antidepressants and psychotherapy, can be further enhanced when someone is also being physically active or having an exercise snack. So to answer your question, what I'm saying is there are many ways we can support our patients and many ways we can encourage them to have better management and control over their distress-- why there is anxiety, depression, sleep disturbances. It's really meeting people where they're at-- which Ms. Mansfield also mentioned, starting somewhere.

So when we see patients in our clinic-- and I've been known to do this, and I've done this back in the day where we would really write a lot more paper prescriptions. But even as part of my discussion points and patient instructions, I always make a point of writing, "Do some physical activity, even minimum opportunity to get yourself moving." Because what we're trying to really do is help with the circulation-- help with the circulation in the body, in the brain, really ramp up those neurotransmitters that help people feel better, remove the unhealthy oxygen, introduce the healthier oxygen. And that, in conjunction with medications, in conjunction with different psychotherapy modalities, in conjunction with progressive muscle relaxation, mindfulness, grounding techniques, can really help people feel less helpless, less stuck, less tired-- again, as I mentioned earlier, less alone, and find opportunities where they have more of a sense of control because that's part of what we're talking about here. There's a strong feeling of helplessness and lack of control when someone is diagnosed with cancer and undergoes cancer care. And this is an opportunity to help them find ways to manage their health physically, mentally, cognitively, spiritually, and feel less a sense of helplessness.

It’s really encouraging me to say that there are many patients who are physically really suffering, whether it's from neuropathic pain, cancer-related fatigue, any kinds of deconditioning related to surgical interventions, other effects of chemotherapies, from depression. And it is much, much harder. And people sometimes cannot physically move. And it requires a lot more activation energy to take those steps. So part of what we do in my clinic and how we partner with our colleagues in palliative medicine as well is how can we manage people's symptoms? How can we manage their depressive symptoms, their physical symptoms? How can we help them be more cognitively stable and intact to be able to safely take those steps or to have more of that motivation or that energy or that pain relief to be able to participate in the things that we're talking about? I'm cognizant of the fact that when we have our patients and family members and caregivers listen to this, there may be some folks who are like, "But I just can't." And I have patients who tell me, "I get it, Dr. Lahijani. I understand. And I appreciate this guidance that you've offered me and the recommendations to use this medication or to consider this, but I just can't." So that problem with motivation and lack of optimal symptom management really has to be addressed in parallel, in my opinion, to really help support patients in actually participating in what we're suggesting here.

Sami Mansfield: I think that's not only an excellent point, I think you really reiterate the partnership that needs to happen with the clinicians and the exercise oncology field or oncology rehab field because the only way to really do this effectively again, and especially a more complex patient, is in conjunction with one another. And I think that we need to be mindful and remind the patients, and like you said, the family members listening, that the conversation should be had, but the clinicians really can help manage the clinical symptoms so that the exercise or rehab professionals can really get in with that, the more implementation piece, when reasonable. But I think we need to take the guilt off our patients that it's not going to be every day, even though they want to. And that's the reality, and that is okay. And some days, it is a rest day or a rest week. And that is part of the healing process of the body and a really important way to recover. And that's okay, too. I think recommendations are nice as an example. But at the end of the day, if they're not reasonable for people, we need to also take that next layer of guilt away. And they just need to be able to feel comfortable and pain-free and symptoms-managed. And that's quality of life as well.

Brielle Gregory Collins: Wow, what a great discussion. And I think the main takeaway here for anyone listening is your health care team is there to help you, and they'll work with you to figure out what's best for you, whatever that might be. So thank you so much. That was wonderful to hear both of your perspectives. And I want to talk a little bit about resources that people listening can turn to to learn a little bit more about this. So I'd like to direct this to both of you. Ms. Mansfield, we'll start with you, but where can people go to learn more about exercise and managing the mental and emotional effects of cancer?

Sami Mansfield: Absolutely. That is the key question is, what next? Really, Cancer.Net is a wonderful and evolving resource and is continuing to progress its information. So no matter when you're listening to this podcast, check out Cancer.Net. I know that the information is online. There's a ton of resources right there. There are some other really great programs and resources. I would talk to your clinicians about things like cancer-specific rehab programs that you may have access to, which many have insurance coverage. And I tell people you don't have to feel broken to get cancer rehab. There are a lot of ways that cancer rehab can help you even just manage general fatigue or cognition. Referral to a speech-language pathologist can be helpful with some of those techniques about memory and chemobrain. So those are resources. In addition, there are qualified exercise professionals through the American College of Sports Medicine that have training and certifications and have experience. That can be another resource that can help you. I would also advise people to think, "You don't always have to have a cancer professional." There are great fitness professionals that may fit-- yoga professionals or other types of exercise modalities. So don't always feel like you have to find the “cancer person.” But depending on your symptoms or side effects, having a professional that understands what it means when you say neuropathy can be very helpful. So I would definitely start with those resources first and then branch out as you feel comfortable.

Dr. Sheila Lahijani: She responded to that question beautifully. And to add to what she just shared, looking at what your own cancer center, your place of health care where you receive it, what's available. There are many websites through the different cancer centers and medical centers that have wonderful patient-facing and family-facing educational resources. The American Cancer Society also has a lot of helpful information. As Ms. Mansfield mentioned, Cancer.Net is a wonderful resource. And also to emphasize that there are programs that can be done virtually, especially in this era of this pandemic. While we encourage in-person interactions, however it's safe and feasible because there's so much benefit to feeling less alone and isolated and maybe having that direct 1-on-1 attention, we recognize that many patients because of their immune compromise or because of whatever challenges they may have with respect to support or transportation or finances, whatever it may be, it might be harder to access care or services where someone lives. And so there are programs and services that are available online. And that shouldn't be limiting. That should be something to really think about and consider.

Actually, I was in a meeting recently where I learned about an organization called the Maple Tree Cancer Alliance, which has programs available through different cancer centers as well, among which is my center, Stanford. And so there are plenty of resources available. And with that, I will also say pick something. Choose something. You don't need to look at everything and try to do everything. Take a look at what's available to you, what's accessible to you, what makes sense, and just try it out, and see if it helps. And if it doesn't help or if it's not providing you any kind of immediate benefit, look to see what other options there are. We have so many patients tell us that they're trying to follow through on our recommendations, and people want to be, quote-unquote, "good patients." And that can get very overwhelming. People in large part want to feel better. They want to get better. That doesn't mean you have to take advantage of every single resource or recommendation that's being offered to you. Take a look at what's close to you, what you can access, and how you can make it work, and start somewhere.

Brielle Gregory Collins: Absolutely.

Sami Mansfield: And on that start somewhere, the other thing to really think about too - and Dr. Lahijani really said this - is you don't have to do-- everything at once can be so overwhelming. This is the long game. And so this exercise piece should be a lifestyle behavioral change piece that works for you in the long-term. It isn't about just, "Here I am. I want to get through just this 1 specific piece in my life." Look for something that you enjoy because you're going to be much more likely to continue. And then thinking about that support circle, it may be someone that has a similar diagnosis or understands what you're going through or have gone through. And it may be somebody that you have met or a family member that has never experienced this but is that person that you can vent to or is your accountability partner or your meet-for-a-walk or a virtual walk partner. I think we need to be really mindful, be creative about this. It should be enjoyable. It should be something that fits you. And at the end of the day, there's no right way to exercise. I think we'd all do something different here today if we all could choose. And that's okay too. Cancer is very individual, and so is this piece of that. So I think that's really empowering for all of our listeners to remember.

Brielle Gregory Collins: Definitely. And that's so nice to hear, as far as there's no right way to exercise, I think that's a really helpful way of looking at it. Well, thank you both so much for your time today and for sharing your expertise, Dr. Lahijani and Ms. Mansfield. It was so great having you both.

Sami Mansfield: Thank you so much for having us.

ASCO: Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, members of the Cancer.Net Editorial Board discuss new research in molecular testing, also known as biomarker testing or tumor marker testing, to help guide treatment for people with early-stage non-small cell lung cancer. This podcast is led by Dr. Ryan Gentzler, Dr. Xiuning Le, Dr. Brendan Stiles, and Dr. Vamsidhar Velcheti.

Dr. Gentzler is the director of the Thoracic Oncology Clinical Research Program at the University of Virginia (UVA) and chairs the UVA Cancer Center’s Lung Cancer Translational Research Team. 

Dr. Le is an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Internal Medicine at The University of Texas MD Anderson Cancer Center.

Dr. Stiles is chief of thoracic surgery and surgical oncology at Montefiore and Albert Einstein College of Medicine.

Dr. Velcheti is the director of thoracic medical oncology at New York University Langone’s Perlmutter Cancer Center.

View disclosures for Dr. Gentzler, Dr. Le, Dr. Stiles, and Dr. Velcheti on Cancer.Net.

Dr. Gentzler: Thank you, everyone, for joining us. We've got a great group here today, and we're really going to focus on talking about molecular testing in lung cancer. This is a very hot topic. My name is Ryan Gentzler from the University of Virginia. I'm a thoracic medical oncologist. We have Drs. Le, Stiles, and Velcheti with us today. I'd like them to go ahead and introduce themselves, starting with Dr. Le.

Dr. Le: My name is Xiuning Le. I'm an assistant professor. I'm at the MD Anderson Cancer Center here in Houston, Texas. I'm also a medical oncologist. Thank you, Ryan, for inviting us today.

Dr. Stiles: Hey, everybody. I'm Brendan Stiles. I'm a thoracic surgeon. I'm chief of thoracic surgery at Albert Einstein College of Medicine in Montefiore Health System here in the Bronx in New York.

Dr. Gentzler: All right, thanks for joining us. And Dr. Velcheti.

Dr. Velcheti: Thank you, Ryan. I'm Vamsidhar Velcheti. I'm the director of the thoracic oncology program at NYU.

Dr. Gentzler: All right, great. We hear a lot of terms thrown around about molecular testing, genomic testing, biomarkers, oncogenic drivers, and I thought it would be good to just define what exactly is molecular testing, so all of our listeners are aware of what we're talking about. Dr. Le, do you want to take this question?

Dr. Le: Yeah. So we have many terms, as you described. In my eyes, there are 2 sets of testing, and then some of them also classify into actionable versus not actionable. So for clinical use, we usually ask the tumor to be tested for both the mutations as well as the immune marker. Usually, the panel of mutational testing is more than a field. Usually, it's depending on the platform we're using, oftentimes in the hundreds of things. And then the immune markers, usually, we refer to PD-L1 and the tumor mutational burden. Those are the 2 commonly used markers now in the clinic. Some of those markers, especially the hundreds in gene testing, not all of them can lead to a clinical decision because we're still in the phase of understanding the interactions of different genes. However, there is a subgroup of those mutations. Nowadays, we have targeted therapy for, we call those actionable mutations. So in the clinic, we push for testing for a panel of mutations as well as immune markers, hoping to look at the tumor comprehensively so that we can recommend a good treatment regimen precise to that particular tumor, precise to that particular patient.

Dr. Gentzler: Yeah. Wonderful. This has also been termed precision medicine, where we really match a therapy to a specific genomic abnormality identified on these tests and maybe, Dr. Velcheti, if you could maybe elaborate on some of the different ways that these tests are performed and how we're using these in clinic today?

Dr. Velcheti: Yeah, definitely. I think our understanding of the biology of lung cancer has evolved quite dramatically over the past several years and obviously it’s led to a lot of advancements in terms of treatment opportunities for patients. Broadly, the way I look at biomarkers in lung cancer or, for that matter, any cancer, it's like you have biomarkers that actually kind of give us very deep insights into the biology of the cancer and giving us insights into how aggressive somebody's cancer is. Those are called prognostic biomarkers, kind of predicting outcome. And there are predictive biomarkers where there are certain biomarkers. If you do have some of these biomarkers in the tumor, then you could potentially use certain treatments that might work better for patients who have those biomarkers. So now we have a lot of different approaches in terms of how we kind of test for these biomarkers. Especially in lung cancer, now we have a lot of new therapeutics for certain genomically categorized types of lung cancer.

And the challenge now is that we have so many different mutations we absolutely need that information to decide on treatment. So how do we test that? Until a few years ago, we've been doing a single gene testing. The problem with those approaches is that we have so many different genes we need to test and we kind of do sequential gene testing, a single gene testing, we won't get all the information we need to make the right decision for our patients. So the standard approach in most oncology practices, especially larger cancer centers and academic medical centers, is do comprehensive genomic profiling, and that's being widely accepted as a standard approach right now.

Dr. Gentzler: Wonderful. And this has really been something that has fallen on the laps of thoracic medical oncologists as we've treated patients with advanced stage or stage 4 disease. And this is starting to become more and more important and relevant for surgeons. And Dr. Stiles, I just wanted to bring you into the conversation and see if this is something that, prior to some of the more recent data, which we'll discuss in a minute, is this something that as a surgeon, you've kept up with and think it's important in a surgical practice?

Dr. Stiles: Yeah, definitely, Ryan. And I think now is probably the most exciting time for that, right? We used to just be sort of in the prognostic side, like Vamsi said, but now we really are in the predictive side in the early-stage disease. And I think that's why everybody is so excited. But that's why there's now this pressure about the timing of biomarker testing. What do you get? Do you get a whole panel? As we'll talk about some of the trials that have made their way into earlier stage disease, but it becomes inherent upon surgeons to really think about this and understand this, from the first time that they meet the patient I think, as we increasingly get better therapies in earlier stage disease.

Dr. Gentzler: So as this has moved into earlier stage disease, a lot of this has been driven by some new data from clinical trials, and Dr. Velcheti, I thought maybe you could comment on the IMpower010 trial and its relevance and why molecular testing is important in the context of that trial.

Dr. Velcheti: Yes, absolutely. I think the IMpower010 Trial is certainly a new shift in our approach to treating stage I, II curable non-small cell lung cancers. So we haven't had an approval in the adjuvant setting in a while. I mean, of course, we had approval with the osimertinib result of the ADAURA trial, but that's only for EGFR patients. Now we have approval for using immunotherapy in the postoperative adjuvant setting for patients with any level of PD-L1 expression. So this is a large randomized study looking at the role of adjuvant atezolizumab, which is a PD-L1 inhibitor in patients who have PD-L1 expression greater than 1%. Patients were randomized getting platinum doublet alone, which is a standard-of-care adjuvant assistant therapy for patients at stage I, II lung cancer. It is atezolizumab at a dose of 1,200 milligrams given every 3 weeks. Patients who received atezolizumab had significantly improved outcomes in disease-free survival. And the benefit was actually really striking for patients who had high PD-L1, patients with PD-L1 testing TPS score of greater than 50%. They had a really remarkable increase in terms of disease-free survival for those patients. So this is certainly very encouraging. And of course, we know it's now approved. We are still awaiting some overall survival results to mature. But given the extent of the benefits we're seeing with the disease-free survival, I think it's a very promising approach.

Dr. Gentzler: Yeah, so obviously, immune therapy has had a tremendous benefit in the adjuvant setting from this trial and still some longer-term follow-up that's needed. But I think the important point here is that molecular testing may identify certain mutations that may make patients less likely to benefit or respond, or perhaps there's more appropriate treatments than immunotherapy within this group. And that brings us to the next trial that I think really shifted this discussion stage with the ADAURA trial. Maybe Dr. Le, if you could summarize this trial and give us your thoughts on why molecular testing is so important in the era of ADAURA.

Dr. Le: Yeah. So ADAURA trial is also an adjuvant trial, meaning that the patient received additional treatment after the completion of surgery. So ADAURA trial looked at patients who have EGFR mutations. So it's a different biomarker. It's a gene biomarker, not the immune biomarker. So this is a large international trial, enrolled almost 700 patients and then randomized the patients after surgery, after standard chemo, the patient can go on to either receive 3 years of osimertinib, which is the standard-of-care therapy for EGFR mutant patients for metastatic setting, or the control group if the patient just received standard of care, which is to continue the monitoring. The trial actually showed that for people who had osimertinib before that prolonged time of 3 years, the risk of the disease coming back is almost 5 times lower than the patient who did not receive therapy. So based on that really striking benefit of after surgery, after chemotherapy, continue osimertinib in EGFR patients, FDA approved after the surgical resection and all the standard care patient can go on for osimertinib for a prolonged time, which we think currently the data is saying the disease is more likely not to come back. And hopefully, in the future, that result will translate into overall survival benefit.

Dr. Gentzler: Okay, wonderful. And I think both of these trials, both the ADAURA and the IMpower010, are adjuvant trials. So these are trials that allow us adequate time to do molecular testing on a large surgical specimen, formulate our plans, and implement those plans up to a month or longer after surgery. Obviously, there's some new data that we've seen in a press release from the CheckMate 816 trial. This is a neoadjuvant trial of chemotherapy plus nivolumab. We've seen previous data from this trial showing some results, but this moves the conversation into the neoadjuvant space, and Dr. Stiles, I wonder if you could give us a summary of your thoughts on the CheckMate 816 and the relevance for molecular testing in that context of neoadjuvant therapy.

Dr. Stiles: Yeah. Thanks, Ryan. I think, first of all, those are incredibly important adjuvant trials. I saw 2 patients each this week on adjuvant osimertinib and adjuvant atezo [atezolizumab], so it's real-life practice. Every day, it's going to benefit patients. But I think that's easy, like you said, these are big specimens that are taken out. You've got time to decide while the patient gets better. Now, we have to shift all this even earlier because CheckMate 816 really has some pretty impressive results. We, unfortunately, don't have the paper yet. I'm told it's going to be coming out soon, but the primary endpoint pathologic complete response 24% versus 2.2%. That's with chemo-nivo versus chemo alone. Obviously, people are questioning, does pathologic complete response correlate with outcomes? Certainly, we got a signal on a press release that the event-free survival is going to be the hazard ratio is 0.63, so it sounds like it does, and I think we'll see more data on that in the next couple of months. A difference in median event-free survival of 32 months versus 21 months in the report. So everybody is excited to see this. And I think it has some advantages over the adjuvant strategy. First of all, more patients are able to tolerate it. It's just 3 cycles, and so it's not given indeterminately for a year.

And it worked across different subgroups. And we can talk about some of the nuances, but as where atezo [atezolizumab] was only looking good in the PD-L1-high. This sort of worked across different groups. The caveat to that is we don't really know what happens with these EGFR patients who are eligible and sort of, how do we then move that test? And all of a sudden, we've got to make a decision on neoadjuvant therapy. Now we need to know. It helps to know the PD-L1 maybe preoperatively, with the high PD-L1, maybe you could wait until adjuvant therapy, with the low to sort of medium PD-L1, maybe you want to give them their shot in the neoadjuvant space. But if they have an EGFR mutation, it's probably not the right thing. We don't really know the data on that and CheckMate 816 yet, but certainly, I'd be sort of hesitant to give them neoadjuvant chemoimmunotherapy. So then you have to teach surgeons all this too, and teach them to think about this and teach them to hold their horses on taking patients to the operating room while they wait for molecular testing. But that probably means we need to speed up the process somewhat either with sort of more rapid turnaround test, with consideration of liquid tests in some instances. It's just an incredibly fast-changing place that here we are speaking about a trial that hasn't even been published yet, so that tells you how fast things are happening.

Dr. Gentzler: One last question. How can the results of these tests guide therapy after surgery? Do we incorporate a full NGS [next-generation sequencing] panel at the time of surgery? And we don't have data on adjuvant therapy for ALK or ROS1, or RET. Do we factor that into how we think about adjuvant chemotherapy, adjuvant immunotherapy, do we employ targeted therapies for some of these mutations? Any thoughts on that?

Dr. Le: Ryan, I think you bring an important point in that EGFR is 1 of the 8 actionable mutations we have nowadays based on FDA and NCCN. The tumor biology between EGFR and ALK-fusion oncogenesis and potential response and benefits probably share some similarities. So we look forward to seeing trials reporting out the adjuvant setting with ALK inhibitors with ROS1. And the smaller target might require a multi-institutional or co-op group effort to really achieve the sample size for us to see. But as of now, we don't have the approval. We try to enroll patients to the oncogene trials, but I think currently we're practicing based on EGFR and PD-L1.

Dr. Stiles: Yes, and I agree. I'm excited to see what comes out of some of those trials. They're slow to grow, but we'll eventually get some readouts. I think an interesting question sometimes is PD-L1. And we had an example recently where in the pre-op biopsy, the patient had a low PD-L1, and so not particularly enthusiastic. And the question sometimes arises, do you test that whole tumor to consider them as kind of an adjuvant to atezo [atezolizumab]and then the fully resected tumor, the PD-L1 was greater than 50%. And so I would sort of sound a caution that the small biopsy sample, they're incredibly helpful for many things, incredibly helpful for moleculars. It may not always be totally representative of the PD-L1 staining.

Dr. Gentzler: And I think that's a good point. Even for molecular testing, sometimes if you have smaller biopsies, you may get a result that's negative, but it could be low levels of DNA and not sufficient to complete the full panel with high quality. So you really have to pay attention to the report and make sure that there's some confidence in the amount of DNA in some of these results.

Well, I think that's all the time we have here, so I appreciate everyone's participation, and hopefully we're able to learn a little bit about genomic testing today.

ASCO: Thank you, Dr. Gentzler, Dr. Le, Dr. Stiles, and Dr. Velcheti. Learn more about treating lung cancer at www.cancer.net/lung. 

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Brielle Gregory: Hi, everyone. I'm Brielle Gregory, a member of the Cancer.Net content team, and I'll be your host for today's Cancer.Net podcast. Cancer.Net is the patient information website of ASCO, the American Society of Clinical Oncology. Today we're going to be talking about hepatitis B virus. Our guests are Dr. Andrew Artz and Dr. Jessica Hwang. Dr. Artz is an associate clinical professor in the Department of Hematology and Hematopoietic Cell Transplantation, the director of the Program for Aging and Blood Cancers, and the deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center in Duarte, California. Dr. Hwang is a tenured professor in the Department of General Internal Medicine in the Division of Internal Medicine at the University of Texas MD Anderson Cancer Center in Houston, Texas. Thanks for joining us today, Dr. Artz and Dr. Hwang.

Dr. Hwang: Thank you, Brielle. Nice to be here.

Dr. Artz: Yes. Likewise, Brielle. Thank you so much.

Brielle Gregory: Today ASCO is publishing a new provisional clinical opinion on hepatitis B virus screening and management for patients with cancer prior to therapy. Dr. Artz and Dr. Hwang served as the co-chairs for this provisional clinical opinion. Before we begin, we should mention that Dr. Artz has no relationships to disclose related to this provisional clinical opinion and Dr. Hwang has one relationship to disclose. Their full disclosure statements can be found on Cancer.Net.

Now, let's talk a little bit about what this provisional clinical opinion means for people with cancer and those who care for them. Dr. Artz, to begin, what is a provisional clinical opinion and how does it influence cancer care?

Dr. Artz; Yes. Absolutely. We appreciate that new information develops very quickly in oncology, and provisional clinical opinions are really a way to respond to the rapid information accumulation in the field. They're evidence-based guidances, and they're meant to offer timely direction to the ASCO membership, which means the physicians and the other providers in the oncology team. Usually it follows practice-changing information, and then there may be updates. Such is the case for this PCO, which was initiated in 2010, updated in 2015, and now we have the next version, the 2020 update that we're discussing today.

Brielle Gregory: So basically, these opinions are updates with the latest information to make sure that patients are getting the most up-to-date care as possible. Is that correct?

Dr. Artz: Yes. Absolutely.

Brielle Gregory: And Dr. Hwang, can you define for us what hepatitis B virus is and how it's connected to cancer?

Dr. Hwang: Hepatitis B virus infects the liver. In an acute setting, it can cause jaundice or yellowing of the eyes, yellowing of the skin, nausea, vomiting, abdominal pain. So that's really the acute phase. But oftentimes hepatitis can infect a person and not even cause any symptoms. This is a troublesome virus that can infect the liver, and once it infects the liver, it can live latently or very quietly in the liver for a long time, and maybe sometimes not even cause problems in certain people. But it can cause some really serious problems, like cirrhosis, which is hardening of the liver. It can even lead to liver cancer and a lot of complications from that because it's very difficult to control at that point.

But what I want to bring to mind today in our discussion is that hepatitis B can linger in a person's liver once infected. And should that person require some sorts of medication that would weaken the immune system - say, for instance, cancer treatments or chemotherapy or one of the newer agents - it's possible that a person's weakened immune system would allow the virus to just start growing and replicating and not be checked. And that can lead to liver complications during, as well as after, that cancer treatment.

Brielle Gregory: Thank you so much for explaining that. So going a little bit into this update, who should be screened for hepatitis B virus and when should people be screened?

Dr. Hwang: Well, that's a really important point, and one that we want to highlight today. Dr. Artz and I were able to participate in a group of really experienced clinicians to try to figure out who should be screened and how best to screen them. And the group really thinks that everybody should be screened who is about to get cancer therapy. So really all patients with any type of cancer, whether it's a cancer that affects a solid organ of the body or perhaps one of the blood cancer conditions. Any patient with any type of cancer really is at risk of having a potential complication if they have hepatitis B, so we just advocate that everybody get screened. It's just a simple blood test, and there are 3 hepatitis B blood tests, and they are routine tests available at all labs, and they're fairly easy to get and the results are available rapidly. So I think it's really just a good practice to get everybody tested before they start their cancer therapy so that they can be well protected.

Brielle Gregory: And I know you mentioned that there are 3 tests for hepatitis B. So can you describe what those 3 tests are?

Dr. Hwang: Sure. One test is called the hepatitis B surface antigen. And if this test is positive, this really is indicative of a patient having one of the more severe forms of hepatitis B, what we talk about in the medical world as being chronic hepatitis B. Another test is called a hepatitis B core antibody, and this is a test that's positive in anybody who's had a past infection with hepatitis B. So it can be positive in patients with chronic disease, but assuredly it is positive in patients with past infection. And then the third test is a test called hepatitis B surface antibody, and that's a protective antibody. It's good to have that one positive. So if a person has had a previous vaccination, this hepatitis B surface antibody will hopefully be positive and indicate that they are protected against the hepatitis B.

Brielle Gregory: And what are some of the problems that hepatitis B can cause during cancer treatment?

Dr. Hwang: Well, Brielle, I mentioned just a few minutes ago that once infected, the hepatitis B virus can linger in the liver of an infected person. And though it might not cause problems, I think that the cancer treatments, if they're immunosuppressive and they weaken a person's immune system, that could lead to the virus replicating and growing out of control, so that it could then lead to liver damage, what we call flares of the liver. It could also lead to really acute liver injury, even liver failure. And there are reports of death from liver-related complications in patients with cancer and underlying hepatitis B from their cancer therapy. So it's a really serious, potentially serious condition, this hepatitis B reactivation that we're talking about, and I think that's why it's really important for patients to be tested for hepatitis B before they receive their cancer treatment.

Brielle Gregory: Thank you so much for explaining that. And Dr. Artz, for people who have previously had hepatitis B, as Dr. Hwang just mentioned, there is a risk that some cancer treatments could lead to a hepatitis B reactivation. So what does ASCO recommend to help reduce that risk of reactivation?

Dr. Artz: Yes. I think it's a really important point for this virus that through appropriate monitoring and treatment, we can largely avoid the complications that were just discussed. And that's really the key point why testing is so important, that it's not only to identify problems that might emerge, but that we have an approach that is likely, for many patients, to avoid complications. Specifically, there are pill or oral medications that are well tolerated, don't interact with most chemotherapy, that would be offered to most patients with what we call chronic hepatitis B—that is, hepatitis B surface antigen—receiving anti-cancer therapies that are systemic—that is, pills or IV chemotherapy—would receive a treatment to prevent chronic hepatitis B from worsening. With some exceptions, in patients receiving hormone therapy alone for prostate cancer or breast cancer—those are some special circumstances where that has to be discussed with an HBV specialist.

Now, for another group of patients, those who had past hepatitis B where the danger of hepatitis B re-emerging is less, we recommend the treatment against hepatitis B in those cases where the treatments the patients will receive weaken the immune system to such a degree that the hepatitis B might re-emerge even in that situation. And those are what we call anti-CD20 antibodies, such as rituximab or stem cell transplant, are the ones that we're most concerned about. But in addition to the medications against hepatitis B, monitoring is a major part of this. So patients who are on medications—or even if they're not on medications, we've outlined a monitoring strategy for clinicians to follow that informs people about the tests, the blood tests they should get, and also to monitor patients past the time of completing chemotherapy because the virus can reactivate even after stopping therapy. And that's really important to know for people.

I think another key point is that in this PCO, we really talk about a collaborative approach, and HBV—now that we'll be identifying it more often, a lot of times patients and clinicians were unaware of its presence. We need to work with HBV specialists—that is, those who have a lot of expertise in HBV in certain situations as a team. And I think that collaborative approach, for situations that are more challenging and we need a more nuanced approach, will allow patients to receive individualized care that's based on their situation.

Brielle Gregory: So just to clarify, both for patients who currently have hepatitis B and patients who have in the past had hepatitis B, there are options for them to hopefully avoid some of the problems that were discussed earlier. Is that correct?

Dr. Artz: Yes. Absolutely. I think identifying hepatitis B is an opportunity to avoid future problems and really safely receive their chemotherapy with fewer complications, or less chance of complications from hepatitis B.

Brielle Gregory: Great. Well, thank you so much for your time and for sharing your expertise today, Dr. Artz and Dr. Hwang. It was so great having you.

Dr. Hwang: It's been a pleasure. Thanks, Brielle.

Dr. Artz: Yeah. It's been a real pleasure. Thank you again.

ASCO: If this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

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ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

The European Society for Medical Oncology 2019 Congress was held in Barcelona, Spain, from September 27 to October 1. In this podcast, Dr. Ricardo Cubedo shares highlights from the meeting, including treatment advances in ovarian and lung cancer. He also discusses a new type of clinical trial known as “basket trials” and the ways they are changing the shape of cancer research.

Dr. Cubedo is the Head of Sarcomas and Hereditary Cancer with the Medical Oncology Service at MD Anderson Cancer Center Madrid. He is also a member of the Cancer.Net Editorial Board.

ASCO would like to thank Dr. Cubedo for discussing this research.

Dr. Ricardo Cubedo: Good day, everybody. My name is Dr. Ricardo Cubedo. I am a medical oncologist from Madrid, Spain, from MD Anderson Cancer Center Madrid, and I was among the 25,000 attendees coming from all around the world, attending the last European Society for Medical Oncology Meeting, which took place between 27 September and 1st of October in Barcelona, which is a very beautiful Spanish city by the Mediterranean sea. We had a record-breaking 3,900 scientific communications, so you can bet that there is a lot to choose from, but I have chosen for you 3 topics. Two of them are relevant on their own, and very important results, and the last 1 I think it goes beyond the results themselves, changing the way we figure out things in order to fight cancer.

The first item is the results of the PAOLA-1 trial, focused on advanced ovarian cancer patients. You know that ovarian cancer is the most lethal gynecological cancers, because we cannot cure it when it is diagnosed too late to remove it, usually because it is too widespread within the belly. Nowadays, those patients rely on chemotherapy in order to stop the disease, control their symptoms, and live longer. We usually use chemotherapeutics based on platinum as front-line treatment, which are just too toxic to use all the time. So the way we do it, we give the chemotherapy for some months, then stop, then used again when the disease starts progressing and the patient becomes symptomatic. Those months between one chemo period and the next one, are precious for ovarian cancer patients, because they can enjoy them free from both the burden of progressing disease and the side effects of platinum chemotherapy.

The new drug that was the center of the PAOLA-1 trial is called olaparib. It is a new non-chemotherapy drug that targets directly the DNA of the tumor cells. And what it does is to prevent the DNA in the tumor cell from repairing itself when it is damaged, and that ultimately leads to the death of the tumor cell. What PAOLA-1 researchers really wanted to know is if olaparib, the new drug, was useful to delay progression once the disease was already stabilized by chemotherapy, giving patients a longer period free from chemo between 1 treatment and the next 1. That seemed a good idea, because olaparib is given as pills and has few side effects. 800, more or less, ovarian cancer patients were recruited into the trial from several countries all across Europe and were divided into 2 groups. Group number 1 were treated in the standard fashion: that is, chemotherapy until the tumor stopped, and then, maintenance with a drug called bevacizumab, which already been proven to delay the need for further chemotherapy. That is the standard. In the group B, the second group, that was the experimental group, olaparib, the new drug, was used on top of the standard treatment. Once the disease was [ceased?] with chemotherapy, patients were put on olaparib, and the results were impressive. In the control group, the median time that the cancer took to reactivate was 16 months, one-six, but the group of women treated with Olaparib didn’t need further chemotherapy for a period just shy of 2 years. Researchers even spotted a group of patients with certain mutations in the tumor DNA that achieved an astounding 37-month progression-free survival. Being able to delay a new period of chemotherapy for over 3 years is a big, big improvement for women with advanced ovarian cancer, and a very welcome new tool in our weaponry against the disease.

That was the first item I wanted to discuss with you. The second one is also a clinical trial, a big clinical trial, called CheckMate 227. You know, we oncologists like to give trials those funny names. This is a trial for lung cancer patients. It is a very large study. It is still ongoing in over 300 hospitals all over the world, also in America. The non-small cell variety of lung cancer is the most common subtype of the disease and a really ruthless one. Lung cancer kills, every year, more Europeans or Americans than any other malignant tumor. So it’s no wonder that huge resources are devoted to research against this beast. Being such an aggressive disease, equally aggressive chemotherapy has been the cornerstone of its treatment, when the tumor has grown or spread beyond the reach of surgery. Again, the problem is that such overaggressive treatments like combination chemotherapy with 2 or 3 drugs at the same time, might put a temporary break on the disease but unfortunately at the expense of quality of life.

What the CheckMate 227 trial explores is the role of immunotherapy. Immunotherapy, I am sure you have heard about it, is a new field of anticancer drugs, non-chemotherapy drugs, that do not attack cancer cell themselves but, instead, use some kind of molecular trickery to shake our own immune system against the tumor. The combination of 2 of such immunotherapeutic drugs, which are called nivolumab and ipilimumab, was compared in this trial to standard chemotherapy. So 1 group received the usual chemotherapy, and the other group received no chemotherapy at all, but those 2 immunotherapeutic agents combined.

The results were eagerly awaited, probably the most expected results in the whole meeting, and were disclosed in Barcelona amidst much expectation at a fully packed hangar-sized conference room. The full size of the trial is suspected to be north of 2,000 individuals, but we already know what happened to the first 800 group of patients during a 2-year period, and the results are quite encouraging. Unfortunately, non-small cell lung cancer is still a deadly disease, because no matter which treatment patients received within the trial, less than half of them were still alive at the 2-year mark. But while only one-third of the patients treated with current state-of-the-art chemotherapy were alive 2 years after treatment, 40% reached the 2-year bar among those treated with immunotherapy. Moreover, and more importantly, there were hints of a small group within that 40%, approximately 2 out of every 10 patients, that stabilized for long periods of time. Something very similar, stabilization, was observed some years ago, when we started to use immunotherapy in melanoma patients. And we now know that many of those patients, stabilizing for many years, are now in fact cured, even with extensive metastasis widespread into many organs. So at first glance, CheckMate 227 results might not seem much, but they mean that, for the first time, we have proved we can treat advanced lung cancer patients without a single drop of chemotherapy, which means much better quality of life. And we have, also for the first time, a realistic prospect for a cure, more beyond mere wishful thinking.

So we have seen the results of a couple of trials which are what we call “practice changing,” which means that many ovarian or lung cancer patients worldwide, should be treated in a different way, with better results, as soon as their oncologists attending the meeting fly back to their working sites.

Lastly, the third piece of information I would like to share with you proves we are now right in the middle of a medical revolution. It’s not surprising if I tell you that the first thing an oncologist like me will try to figure out when faced with a new advanced cancer case is where it comes from, because we do not equally treat a breast cancer case, a stomach cancer, or lung cancer. Well, it has been so until recently. During the last decade we have learnt quite a bit about the nuts and bolts of cancer. Specific gene mutations and wrecked proteins are both the hallmarks of cancer cells and targets for new drugs. I will give you an example: several years ago researchers found a protein called HER2 on the surface of cancer cells in 2 or 3 out of every 10 breast cancer patients. What this protein does is to rev up the cell’s machinery keeping it in constant multiplication and leading to fast tumor growth, so those were patients with very bad prognosis, as the tumor that grows rapidly, also spreads rapidly. But a new drug called trastuzumab was tailored to disable HER2, the protein that was accelerating the tumor cell, and that made a huge leap in the treatment of HER2-positive breast cancer patients. But the white-coated guys at the research labs showed us that HER2 was not only present in breast cancer, but also in subsets of gastric, lung, ovary, womb, bladder, colon, and head and neck tumors, which was quite surprising, because those are completely unrelated malignancies. Nowadays, trastuzumab, the breast cancer drug, is also used to treat gastric tumors and is beginning to raise interest in the lung cancer arena too.

Well, inspired by those facts, some brave oncologists began to think out of the box and wondered if all we really need to know is the mutations and other molecular characteristics of the tumors in order to select treatments targeted against them, no matter where the cancer comes from. To treat in the same way, a colon cancer, a thyroid cancer, a breast cancer, or a brain cancer, provided they have the same molecular basis. Well such ideas were so revolutionary, they raised a few eyebrows and a lot of skepticism, but, well, this is science and we do not dismiss ideas without some previous research. Thus, the so-called “basket trials” were designed and carried out. Patients in such “basket trials” were hand-picked based on specific mutations and put to treatment, just like one chooses ripe berries and collects them into the basket.

The result of such ground-breaking trials proved that the concept was right. In this Barcelona meeting, Dr. Christian Dittrich from Vienna presented us with the combined results of 2 basket studies: the SCOUT and the NAVIGATE trials. Both explore the activity of a new drug called larotrectinib, in patients with any kind of cancer, provided their tumors had a mutant form of a protein called TRK. When healthy, TRK proteins are essential for a healthy brain and nervous system. But once mutated, TRK leads to cancer in several organs. And that was the basis of the trial. The new drug, larotrectinib, is carefully designed to disable the mutated TRK proteins while sparing the healthy ones you need. Both clinical trials combined included, more or less 160 patients, from children under 1 year to 84 year old adults. The results presented at the meeting in Barcelona were rewarded with the general applause from the audience, because they were astounding. 80% of the patients responded to the drug, more than thee-quarters of them still without signs of any health deterioration 1 year after they were given their first dose. Such results are really remarkable, as we are speaking of a group of patients diagnosed with no less than 18 different types of cancer, treated with a single drug, many of them having failed to several previous treatments or resistant to any known therapy.

Those results are not practice changing, because we have to resolve a lot of questions first, but are very exciting because they open a new drug for cancer treatment.

After a good medical meeting you go back home with some answers. But after a really good one you collect many more questions than answers. Are we going to treat patients based on their tumor genetics instead on classical tumor types? How are new treatments to be combined? Which ones should be given frontline, which ones after progression? What genes should be checked in tumor biopsies on a routine basis? Are there late side effects still to be seen from the new drugs? When to stop maintenance treatments? Are some long-lasting responders really cured of their cancer? How are we going to pay for the new ultra-expensive fancy drugs, some of which are to be maintained for years, even lifelong? Many, many questions to answer.

One thing I assure you: these are thrilling times to be an oncologist. I thank you all for your attention.

ASCO: Thank you, Dr. Cubedo.

Listen to more research highlights from scientific meetings: subscribe to Cancer.Net Podcasts on Apple Podcasts or Google Play, or visit www.cancer.net.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

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ASCO: Usted está escuchando un pódcast de Cancer.Net en español. Este sitio web de información sobre el cáncer es producido por la Sociedad Estadounidense de Oncología Clínica, o la American Society of Clinical Oncology en inglés, la organización profesional líder en el mundo para médicos que atienden a personas con cáncer.

El propósito de este pódcast es instruir y brindar información. Esto no es un sustituto de la atención médica profesional y no está previsto que sea utilizado para el diagnóstico o el tratamiento de afecciones individuales. Los invitados de este pódcast expresan sus opiniones, experiencias y conclusiones. La mención de cualquier producto, servicio, organización, actividad o terapia no debe considerarse como aval por parte de la American Society of Clinical Oncology. La investigación sobre el cáncer que se analiza en este pódcast está en curso; por lo tanto, los datos descritos aquí pueden variar a medida que la investigación avanza.

El verano es una época en que las personas suelen hacer comidas, parrilladas y pícnics al aire libre. En este pódcast, las integrantes del personal del Departamento de Agricultura de los Estadios Unidos, Janice López‑Muñoz y Clara Yuvienco, explican por qué la seguridad de los alimentos es particularmente importante para las personas diagnosticadas con cáncer y comparten consejos para evitar enfermedades transmitidas por los alimentos cuando se come al aire libre. Janice López-Muñoz es especialista en relaciones públicas del Servicio de Inocuidad e Inspección de los Alimentos del Departamento de Agricultura de los Estadios Unidos, y Clara Yuvienco es especialista bilingüe en tecnología de la información del Departamento de Agricultura de los Estadios Unidos.

La American Society of Clinical Oncology quiere agradecerles a la señorita López y la señorita Yuvienco por conversar sobre este tema.

Janice López-Muñoz: Hola, bienvenidos a este podcast de Cancer.Net. Les habla Janice López, especialista en asuntos públicos del Departamento de Agricultura de los Estados Unidos. Y hoy me acompaña Clara Yuvienco, especialista en información técnica bilingüe del Departamento de Agricultura de los Estados Unidos. Clara nos estará proporcionando información acerca de la manipulación segura de los alimentos. Bienvenida Clara.

Clara Yuvienco: Muchas gracias Janice, muchas gracias por escucharnos.

Janice López-Muñoz: Vamos a entrar entonces esta mañana al tema, que nos va a estar proveyendo muchísimas recomendaciones, te agradecemos estos datos. Mi primera pregunta hoy sería: ¿por qué las personas con cáncer tienen mayor riesgo de sufrir enfermedades trasmitidas por los alimentos?

Clara Yuvienco: Sí, las personas con cáncer tienen un mayor riesgo de sufrir una enfermedad trasmitida por los alimentos, debido a que su sistema inmunológico está debilitado. Los tratamientos para el cáncer, como la radiación y la quimioterapia, debilitan el sistema inmunológico del cuerpo, al afectar las células sanguíneas que protegen contra de las enfermedades y los gérmenes. Y como resultado, tu cuerpo no puede combatir infecciones, sustancias extrañas, enfermedades, al igual que el cuerpo de una persona que está sana. Debido a este riesgo, las personas con cáncer o quienes preparan los alimentos para ellas, deben practicar técnicas adecuadas de manejo de alimentos para matar los gérmenes, las bacterias, y evitar la contaminación cruzada. Debemos tener en cuenta que las enfermedades trasmitidas por los alimentos, o causadas por el consumo de los alimentos que contienen bacterias o parásitos, pueden ser muy graves y en ocasiones letales, mortales para este tipo de pacientes.

Janice López-Muñoz: Nos mencionas que debemos tener cuidado, tanto las personas que tienen cáncer como aquellos que los cuidan. ¿Cuáles son esos pasos fundamentales que debemos practicar para protegernos de estas enfermedades trasmitidas por los alimentos?

Clara Yuvienco: Gracias por esa pregunta, muy importante. Bueno, el Departamento de Agricultura recomienda cuatro pasos que son fundamentales para evitar enfermarnos por los alimentos. El primero es limpiar, y en este debemos tener en cuenta que antes de empezar a preparar nuestros alimentos o a manipular nuestros alimentos, debemos lavarnos las manos. Debemos asegurarnos de que las superficies y todos los utensilios que vamos a utilizar para preparar los alimentos estén limpios. El segundo, es que debemos separar los alimentos crudos de los que ya están cocidos o listos para comer, y también que debemos separar los vegetales y las frutas de las carnes. El tercero, cocinar: que debemos tener en cuenta que los alimentos, especialmente las carnes, las aves, se deben cocinar, preparar a la temperatura mínima interna recomendada. Y muy importante también, que esta temperatura debe ser medida por un termómetro para alimentos, que es la única forma de garantizar que nuestras carnes, nuestros alimentos, han sido preparados a la temperatura adecuada y que han sido cocidos completamente. El tercero, enfriar: que debemos refrigerar nuestros alimentos dentro de un período de dos horas, si la temperatura es menor de 90 grados, o una hora si es mayor a los 90 grados.

Janice López-Muñoz: Qué interesante. O sea, que son cuatro pasos: limpiar, separar, cocinar y enfriar. Muy fáciles, es cuestión de ponerlos en práctica con toda esta información que nos ha dado en la mañana de hoy. Por ejemplo, estamos en el tiempo de verano, hay muchas actividades de temporada, estamos al aire libre, que podemos por ejemplo tener un pícnic o compartir en algún parque, una barbacoa. ¿Qué suministros o consideraciones, las personas deben seguir a la hora de hacer este tipo de actividad al aire libre?

Clara Yuvienco: Sí, muy importante esta pregunta también. Debemos, primero que todo, tener en cuenta que necesitamos tener agua limpia disponible para lavarnos las manos. Si estamos en el parque, o si estamos en un sitio donde no hay una llave o un grifo disponible para obtener esta agua limpia, que la podemos llevar de nuestras casas para el parque, porque estos pacientes deben tener esta recomendación muy en cuenta. Entonces, el lavado de las manos es la forma más económica, pero algunas veces nos olvidamos; pero es la mejor forma de prevenir la contaminación cruzada, la transferencia de bacterias dañinas de unos alimentos a otros. Y también, por ejemplo, lavar las tablas de cortar y los utensilios que vamos a utilizar. Además, si nosotros tocamos los alimentos con las manos sucias, los gérmenes, las bacterias pueden propagarse, crecer y causar una intoxicación alimentaria. Por eso debemos lavarnos las manos antes de comenzar la preparación de los alimentos, después de manipular las carnes crudas o las aves, los mariscos. O también después de tocar los animales, después de usar el baño, de cambiar los pañales de nuestros bebés, o también después de limpiarnos la nariz, después de toser o de estornudar.

Janice López-Muñoz: O sea, que todas esas son consideraciones donde cobra muchísima importancia mantener nuestras manos limpias, es lo que entendemos. ¿Hay algunos pasos también que sean correctos, o que ustedes recomienden a la hora de lavarnos las manos? ¿Cuáles podrían ser esas recomendaciones que ustedes tienen a la hora de hacer este lavado de mano de manera correcta?

Clara Yuvienco: Sí, tenemos cinco pasos que son muy importantes de seguir a la hora de lavarnos las manos. El primero es mojarnos la manos, luego utilizar jabón y asegurarnos de que ese jabón hace espuma. Luego nos frotamos las manos con este jabón durante más o menos 20 segundos. Nos enjuagamos con agua limpia, y luego nos secamos con una toalla que esté limpia; bien sea una toalla de tela o de papel, pero asegurarnos de que esa toalla está limpia.

Janice López-Muñoz: Qué interesante Clara, excelente información, muchas gracias. Estamos en esta actividad, estamos fuera, al aire libre, estamos lejos de las comodidades de nuestras cocinas. ¿Hay alguna recomendación que ustedes puedan decirnos acerca de, por ejemplo, cómo almacenar de manera correcta estos alimentos que estamos disfrutando en esta actividad?

Clara Yuvienco: Sí, claro. Lo primero que todo es que debemos planear, decidir qué vamos a comer, cómo lo vamos a cocinar y qué utensilios, qué equipo de cocina vamos a necesitar. Debemos tratar de planificar la cantidad de los alimentos perecederos, como, por ejemplo, la carne, el pollo, los huevos, los mariscos, las ensaladas, para que no tengamos demasiados sobrantes. Para que no nos tengamos que preocupar luego de la comida que nos sobra, porque como ya había dicho antes, esta la debemos refrigerar dentro de un período de una a dos horas. También, al calcular la cantidad de alimentos, debemos calcular la cantidad de alimentos que debemos mantener fríos, debemos empacar los alimentos perecederos directamente al refrigerador o congelador en una nevera portátil, con suficiente hielo o paquetes de gel, para asegurarnos de que van a mantener una temperatura de 40 grados Fahrenheit, o sea, 4.4 grados centígrados.

Janice López-Muñoz: Okay. Y entonces, ¿por qué es que eso se requiere de esa manera?

Clara Yuvienco: Bueno, se requiere mantener refrigerados y a estas temperaturas en la nevera portátil, porque las bacterias crecen y se multiplican muy rápidamente en lo que nosotros llamamos "la zona de peligro", que está entre los 40 grados Fahrenheit, o sea, los 4.4 grados centígrados y los 140 grados Fahrenheit, o sea, 60 grados centígrados. Los alimentos que han sido transportados sin una fuente de hielo o han sido dejados al sol, no van a permanecer seguros por mucho tiempo, por eso es muy importante tener esta recomendación muy en cuenta.

Janice López-Muñoz: Qué interesantísimo está este tema. Te pregunto, ¿hay algunas recomendaciones, por ejemplo, cuando estamos transportando esa nevera portátil? ¿La debemos mantener en ciertos lugares específicos? ¿Qué nos puedes comentar sobre eso?

Clara Yuvienco: Sí, debemos tener en cuenta que no deberíamos meter esta nevera portátil en el baúl o en la cajuela del carro, recomendamos que lo llevemos dentro del auto, el cual va a estar en aire acondicionado. Y mientras estamos en el pícnic o en la reunión al aire libre, o en el asado, o mientras caminamos, debemos mantener esta nevera portátil a la sombra. Y debemos también mantener la tapa cerrada y evitar estarla abriendo y cerrando continuamente. Y también muy importante, si el hielo se derrite debemos reemplazarlo.

Janice López-Muñoz: O sea, que tenemos que tener cantidades de hielo suficientes para mantener siempre eso frío, es lo que queremos decir.

Clara Yuvienco: Y también algo muy importante que olvidé mencionar antes, que podemos colocar un termómetro adentro de la nevera portátil, para asegurarnos de que vamos a mantener esa temperatura, por lo menos a los 40 grados Farenheit, o sea los 4.4 centígrados.

Janice López-Muñoz: O sea, que siempre podemos tener esta información a la mano y asegurarnos que sea así.

Clara Yuvienco: Exacto.     

Janice López-Muñoz: Excelente, es un buen consejito, un buen tip, gracias. ¿Hay algunos alimentos que sean más riesgosos o que puedan causar una intoxicación alimentaria si no los manipulamos adecuadamente, por ejemplo?

Clara Yuvienco: Sí, debemos, por ejemplo, tener en cuenta que debemos evitar las carnes, las aves y los mariscos que estén crudos o que no estén bien cocidos. También, no consumir leche que no sea pasteurizada. Otra cosa, los huevos que no están bien cocidos o que están crudos. Debemos también lavar muy bien las frutas y las verduras. Los quesos que sean suaves, que están hechos o elaborados con leches que no son pasteurizadas, eso también lo deberíamos evitar. Por ejemplo, las salchichas y las carnes frías, que no las deberíamos comer frías, sino calentarlas. Y también, por ejemplo, los gérmenes, como por ejemplo, los gérmenes de frijol, o de alfalfa, estos deberíamos evitarlos al máximo.

Janice López-Muñoz: Durante en este tiempo en que estamos. Interesantísimo por demás, de verdad que ha sido una tremenda información. Sabemos que toda esta información que tenemos aquí disponible en este podcast, la van a estar escuchando. Sin embargo queremos saber dónde las personas, si, digamos, quieren más información, si necesitan hablar con un experto en este tema, ¿dónde podemos encontrar esa información, ya sea en línea, a nivel de llamada? ¿Cómo nos puedes orientar respecto a estas otras fuentes de información?

Clara Yuvienco: Sí, el Departamento de Agricultura cuenta con la línea de información para carnes y aves, la cual está disponible tanto en inglés como en español, de las 10:00 de la mañana a las 6:00 de la tarde, hora del este, lunes a viernes, y allí pueden llamar ustedes al 1-888-674-6854. También tenemos disponible nuestra representante virtual Pregúntale a Karen, que esta está disponible las 24 horas al día, los siete días a la semana. Ustedes nos pueden enviar sus preguntas allí, nosotros se las contestaremos en español, y este está disponible en pregunteleakaren.gov.

Janice López-Muñoz: Perfecto, qué interesante. O sea, que tenemos un servicio en línea, repasando la dirección: pregunteleakaren.gov, y también tenemos entonces el teléfono del Hotline, que si nos lo puedes repetir, por favor.

Clara Yuvienco: Es el 1-888-674-6854, o MPHotline.

Janice López-Muñoz: Perfecto, MPHotline y este teléfono, ustedes contestan las preguntas en español también, ¿correcto?

Clara Yuvienco: Exacto. También el Departamento de Agricultura tiene un sitio web en español, que está disponible en www.usda.gov.

Janice López-Muñoz: Gracias por esta información tan valiosa, Clara, esperamos que sea de muchísimo provecho. Repetimos nuevamente: 1-888-MPHotline, es el número de teléfono para hablar con los expertos. También puede ser de 10:00 de la mañana hasta las 6:00 de la tarde, hora del este. Tenemos también la información sobre el web, que es: www.fsis.usda.gov, y pregunteleakaren.gov, que es donde usted puede charlar en vivo también con los expertos, todo esto en español. Agradecemos su atención a este tema, le agradecemos por escucharnos y estamos siempre a sus órdenes, muchas gracias.

Clara Yuvienco: Muchas gracias. Gracias.

ASCO: Gracias, señorita López y señorita Yuvienco. Encuentre más información de confianza para personas con cáncer en www.cancer.net/es. Y si este pódcast fue útil, tómese un minuto para suscribirse, dar una calificación y escribir una reseña del programa en Apple Podcasts o Google Play.

Cancer.Net está respaldado por Conquer Cancer, la fundación de la American Society of Clinical Oncology que financia la investigación de vanguardia sobre todos los tipos de cáncer para ayudar a pacientes de todo el mundo. Para ayudar con la financiación de Cancer.Net y programas similares, haga su donación en conquer.org/support.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

ASCO’s first clinical trial is the Targeted Agent and Profiling Utilization Registry, or TAPUR Study. This clinical trial is intended for people with advanced cancer without other treatment options available, and whose cancer has at least one genomic variation that can be targeted with specific drugs.

In this podcast, Dr. Richard Schilsky discusses the TAPUR study and explains why it is significant. He also discusses what participants can expect. Dr. Schilsky is the Principal Investigator for the TAPUR study. He is also the former Chief Medical Officer for ASCO and Professor Emeritus at University of Chicago.

View Dr. Schilsky’s disclosures at Cancer.Net.

Dr. Schilsky: Hi, everyone. My name is Richard Schilsky and I'm the principal investigator of the ASCO TAPUR Study and the former Chief Medical Officer of ASCO. I'm happy to give you an overview and update about the study today. By the way, TAPUR is an acronym that stands for Targeted Agent and Profiling Utilization Registry. Hopefully, the reason for naming it that will become clear as you listen. The TAPUR study was conceived in 2013 and launched in 2016, and was based on the observation that there was a rapid increase in testing the tumors of patients with advanced cancer for gene mutations that might be contributing to the growth of the tumor, so-called genomic profiling, in the hope of finding a genomic alteration that could potentially be treated by a drug that was already FDA-approved for a different tumor type than what the patient had.

Meaning, in order for the patient to receive the drug, it would have to be prescribed off-label. The challenge with prescribing the off-label use of a drug is that most insurance plans don't cover the cost of treatment. Additionally, even if the patient were able to receive the drug, there was no mechanism for the oncology community to learn from the patient's treatment experience.

The TAPUR study has managed to address these challenges by providing access to FDA-approved drugs at no cost to the patient and providing treatment results to the oncology community regarding the effects of off-label use of the treatments being studied. Now, TAPUR is a clinical trial, and its primary objective is to describe the anti-tumor activity and toxicity of commercially available targeted anti-cancer drugs prescribed for treatment of patients whose tumors have a genomic alteration known to be a drug target or to predict sensitivity to a drug.

TAPUR was designed to be simple for providers and patients. It's a phase 2 study, meaning that we're aiming to learn about efficacy and safety. It’s prospective, that is, it enrolls patients going forward. It is not randomized. Everybody gets a treatment based on the genomic profile of their tumor and the available treatments in the study. It's a multi-basket study. That is to say, multiple therapies are available on the study that are targeting multiple genomic alterations. And it's a pragmatic study. TAPUR attempts to replicate routine clinical care. It's exempt from FDA oversight. It provides oral drugs that can be shipped directly to the patient's home after the first visit.

Now, as I said, the TAPUR study was launched in March of 2016. And as of this month, it's still going strong, with more than 2,700 patients having been enrolled at 267 locations in 28 states. So how does the study work? Well, a patient's physician has results of a genomic profile of the patient's tumor and determines that a study drug might benefit the patient. The patient then decides to participate in TAPUR and gives their informed consent. A molecular tumor board, which is a group of experts convened by ASCO, is available to consult regarding the proposed treatment or to provide alternative treatment options for the patient. A participating pharmaceutical company, and there are 10 right now, provides the study treatments at no cost to the patient.

The patient is cared for by their own oncologist, receives a standard dose of the drug, and is evaluated at standard intervals to see if the treatment is working and if they're having any side effects. ASCO has convened an independent data and safety monitoring board of cancer experts that periodically reviews results and determines whether treatment is promising for a particular cancer type and genomic alteration. That's what we call a cohort in the study. Once the data are finalized, ASCO publishes the study findings in peer-reviewed journals to inform clinical practice and future research.

So let me give you an example. There are specific molecular alterations that often appear in tumor cells that are important for driving the growth and progression of the cancer and can be targeted with specific drugs that interrupt those abnormal molecular pathways. Many of these alterations occur at low frequency, meaning in less than 5% of tumors of any given type. The benefit of the TAPUR trial having a basket design is our ability to evaluate multiple therapies simultaneously to target multiple low-frequency alterations, which ultimately offers more treatment options to patients who wish to participate in the study.

If the TAPUR study were set up looking to target only a single genomic alteration, we would potentially have to screen hundreds of patients in order to find one who is appropriate for the trial, which also means hundreds more would still be left without treatment options. But because TAPUR evaluates multiple treatments and multiple genomic alterations simultaneously, we found that about two-thirds of patients who were screened for the trial ultimately enroll.

A specific example of a drug and targeted gene alteration on TAPUR is the use of the treatment combination pertuzumab plus trastuzumab in tumors with ErbB2 amplification or mutation. Now, you may be aware that ErbB2 is a gene that is synonymous with the HER2 gene that is frequently amplified or overexpressed in patients with breast cancer. And this drug combination, pertuzumab and trastuzumab, is FDA-approved for treatment of patients with breast cancer. But in the TAPUR study, we found multiple tumor types outside the FDA-approved label that can benefit from this treatment if an ErbB2 alteration is detected, including patients with colorectal cancer, endometrial [uterine] cancer, biliary tract cancer, and lung cancer.

To learn more about TAPUR, please follow our progress at the ASCO website. In an effort to provide up-to-date information about cohorts that are available for enrollment on the TAPUR study, ASCO launched a public-facing status report in March of 2023. So first click on www.tapur.org. Click on the link to the ASCO website. From there, select study participation at the bottom of the page. Once at the study participation page, click on the link to see a list of study cohorts that are currently enrolling. The report updates daily, providing viewers with an up-to-date list of available study cohorts based on their genomic alterations. It's important to note that study cohorts are available on a first-to-enroll basis. You can also find information about current results from the TAPUR study on the study results page.

So what have we learned so far? Thus far, we've publicly reported results on 29 cohorts of patients. 17 gave a positive signal of treatment activity, 12 were negative. Now we feel it's just as important to report on the negative results as the positive results. If the treatment is unlikely to be effective for patients, it's important to inform the oncology community because all of the drugs in the study are commercially available and could be prescribed to a patient.

Enrollment to patients on TAPUR is very representative of the U.S. population. The study has broad eligibility criteria that allows more patients to enroll, including patients with an ECOG performance status of 0 to 2 and younger patients. Some treatments allow for adolescent patients as young as age 12 to be enrolled in the study.

We hope the oncology community finds value in the TAPUR study. Physicians have the opportunity to contribute to research and participate in publications and to contribute more knowledge in the field of oncology. TAPUR provides guidance on interpreting genomic reports via the molecular tumor board and provides additional treatment options for patients. Institutions obtain insights on potential new uses of existing drugs and their side effects, and TAPUR data can inform updates to clinical practice guidelines. And patients receive access to drugs not available as standard of care. Patients may be able to receive oral drugs at their home and limit their commute to clinic.

And of course, participation in the study provides an opportunity for patients themselves to contribute to knowledge about cancer treatments. To find a clinical site offering the TAPUR study, please visit the TAPUR website again, www.tapur.org and select “Participating Centers.” This will lead to a searchable map of participating sites and includes the site-specific contacts. Contact the primary contact listed for that site. Thank you for listening to this update on the ASCO TAPUR study and enjoy the rest of your day.

ASCO: Thank you, Dr. Schilsky. Learn more about clinical trials, including the TAPUR Study, at www.cancer.net/clinicaltrials.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, esophageal cancer survivor Rachael Kearney shares her story with Dr. Frank Penedo, Associate Director of Cancer Survivorship & Behavioral Translational Sciences and the Director of the Cancer Survivorship Program at the University of Miami Sylvester Comprehensive Cancer Center, and an Advisory Panelist on the Cancer.Net Editorial Board.

They discuss her podcast, Call On Courage, which features conversations connected to courage, starting over, and overcoming. They also discuss the value in sharing your story, and tips for people with cancer and survivors.

You can view disclosures for Dr. Penedo and Ms. Kearney at Cancer.Net.

Dr. Frank Penedo: Hello, I am Frank Penedo. I am the associate director of cancer survivorship and behavioral translational sciences and also the director of cancer survivorship and supportive care programs at the University of Miami Sylvester Comprehensive Cancer Center. I'm also an advisory panelist on the Cancer.Net Editorial Board. Today, it is my pleasure to welcome and talk with Rachael Kearney. Rachael is an esophageal cancer survivor who lives in Manchester, England. After she received her cancer diagnosis, Rachael started a podcast called Call On Courage, which features conversations connected to courage, starting over, and overcoming in general. Rachael, thank you so much for talking with us today.

Rachael Kearney: Thanks for having me, Frank. I'm excited to get into this conversation.

Dr. Frank Penedo: Before we begin, Rachael, I should mention that we have no relationship to disclose related to this podcast today. Rachael, can you please tell us a little bit about your experience being diagnosed with cancer and your journey thereafter and what was it like?

Rachael Kearney: Yeah, so this is kind of coming into about 15 months ago. Out of nowhere, I had sort of severe acid reflux. And I was due to meet up with some girlfriends in Manchester, and I was just really struggling to eat my breakfast. It was just bizarre because I've not had those type of symptoms before. And essentially, what happened very quickly, within a 3-week period, this acid reflux increased, and it got worse. And it got to the point where I couldn't tolerate water. So I knew something was seriously up. But there was a waiting period before I got admitted to hospital, before I could have an endoscopy, which is obviously what I knew was going to get to the bottom of things to find out what was going on. And, yeah, it was just very scary in terms of not being able to tolerate normal food. But essentially, when I did get admitted, the endoscopy appointment came a lot quicker within a matter of 2 days, and then the actual diagnosis of esophagus cancer was within 24 hours after that. Obviously, it was just a massive shock because there wasn't a history of this in my family. And at the time, I was only 42. I'm 43 now. And it just felt very bizarre because I hadn't heard of anyone else that had esophagus cancer in my age group or friendship circles or whatever.

Dr. Frank Penedo: Yeah, you mentioned, Rachael, a couple of words in there that stand out. It's just a shock of that diagnosis and, of course, the fear that comes along with that. It sounds like you were able to get proper attention pretty quickly, which is obviously very important when dealing with a cancer diagnosis. But can you tell us a little bit about how you dealt with that initial shock and fear?

Rachael Kearney: So the weird thing was I was in shock, but I wasn't scared. And I don't know why, logically. I don't know why I wasn't struggling with a lot of anxiety. I don't know. There was just this inner sense, that things were going to get treated quite quickly. And, I mean, I had 2 surgeons because-- I don't know what the procedure is like in other countries, but in the UK, the treatment plan was a sandwich of chemotherapy and esophagectomy, and then chemotherapy at the end of that. The esophagectomy is the critical bit because the surgery essentially-- mine was actually an advanced tumor, so it had been there a while. So I knew surgery was the best course of action because this thing had been growing inside of me. And it was like-- it's a drastic surgery, the esophagectomy, because they're obviously removing a chunk of your esophagus, and you're also having essentially a gastric band. I was massively into fitness before I had cancer, so it almost sounds slightly annoying now, but the challenge now is more to focus on getting the calories in. And maintaining good weight is the focus. But that said, I think it was just a lot of-- I was having to process a lot of information because the treatment was coming at me quite quickly. And there was things about it lifestyle-wise that-- because prior to chemotherapy, I was on a feeding tube to get my nutrition. And at the time, I was more concerned that I wouldn't be able to eat in the normal way, that I'd maybe end up long-term on a feeding tube, which was something that was-- you've got all these questions about what your future and your lifestyle looks like post-esophagus cancer, and that was kind of in the mix.

But I think one of the things that was amazing was I had a lot of community, I had a lot of support around me in Manchester. So I was really fortunate, even though there were some wards within the local hospital I was in that were COVID-restricted still in terms of visitors, they made allowance for me to be able to have visitors and stuff like that. So I was really fortunate and even had a friend that worked in the hospital that would come and see me at the end of her shifts and stuff like that. So I had a lot of people checking in when I was in hospital, so I felt very supported through that process. But the thing that's complicated is you're very unwell and you're having to take in lots of information in terms of your treatment plan. And then they can't give you guaranteed scenarios of what your lifestyle is going to look like at the end of surgery. So that's the grey area, really. Yeah.

Dr. Frank Penedo: Sure, Rachael. And cancer in itself, it can be very challenging, let alone during a pandemic, when we have to adjust so many other aspects of our life. But it sounds like you had a pretty good support system, which, as we know, helps our cancer patients and survivors really manage the experience and get through. You touched a little bit upon your treatment. You mentioned it included surgery and reshaping of your esophagus and the stomach. And you touch upon the effects of surgery, which can be persistent. It can really persist well beyond that active treatment period. Can you talk a little bit more about how you've been able to cope with these side effects and changes that you've experienced?

Rachael Kearney: Yeah, so I was a massive foodie before all of this, very food-orientated. Food was almost, in family and friendship circles, a love language. And Manchester's got a thriving food scene out in the city and stuff, so a lot of socializing revolved around food. And I think the great thing about the upper GI ward that I was on at the time is there's no secrets and there's no sugar coating everything. They give you probably sometimes worst-case scenarios in terms of what things might look like after surgery. But the one thing they did say is I would need to have a puree diet moving forward and that would, to all intents and purposes, be permanent as a lifestyle change. They did say I could have these particular-- they're a bit invasive, but dilatation procedures where there's a physical stretching of the esophagus-- what actually happens is if-- once you come out of the surgery and you try to eat food, what's actually happening is things sometimes get caught. So I've got to be really careful about what I eat. I'm now on basically a liquid diet. And for texture, there's certain types of crisps, or, obviously, you guys say chips, that are melty or crackers that are melty in texture. So at least I get some kind of crunch just in terms of what I'm putting into my mouth and stuff. But I'm pretty much living on blended food or soups and ice cream and yogurt and things like that and smoothies. So the diet is massively limited now in terms of what I eat. The dilatations were offered to me as a way to kind of stretch my esophagus to encourage-- it's the swallow that's the challenge.

So if I had something bread-based and tried to eat that, it just gets caught and it just comes straight back up. So I live alone. So I don't try and test the boundaries of what I can eat and what I can't eat because I don't want to risk choking and things like that when I'm at home on my own. And then obviously, in public, there's so little warning if something needs to come back up. Socially, it's just a no-no. So what I have found, 2 things, are, I guess, really making my needs known. So there's a food market in Manchester I went to at the weekend. And there's this amazing Mexican vendor there. And they make things that are not on the menu for me that pureed, amazing, delicious Mexican food that-- they just know what my condition is. And I'm really clear I've had esophagus cancer, and this is the situation.

And then I think the other thing that's really key for me, because when I tell people I'm never going to be able to have pizza again in my life, people look at you and feel really sad because food is such a thing that brings joy. And I was so food-orientated before all of this. But I think I have to keep remembering I was on a feeding tube for 3 and a half months and I wasn't sure if that was going to be my new normal moving forwards. And there's obviously people, even young people, with other medical conditions-- I found these people on social media who live permanently on a feeding tube. Lifestyle-wise, that is so limiting. And I just thought, "Actually, my lifestyle-- it's changed. But I'm still out, I'm still active." I used to throw around kettlebells a lot, but now I'm just doing a lot of walking. So I'm still walking a lot and getting my exercise in. It's just that my diet has gone more simplified, this liquid diet, and I'm grateful that I can taste things and still occasionally have a cocktail. And obviously, the volume of what I can tolerate because of the gastric band side of things is just less in terms of volume. So I just get fuller quickly, as well, just being mindful of that.

Dr. Frank Penedo: Rachael, thank you for sharing that experience. I think we tend to undermine or underestimate what happens after treatment. We're so focused on curing the cancer and having the right level of treatment and getting the best care possible. But you have so eloquently described what experiences one can face after treatment. And these can be very challenging for anyone. Was there anything that surprised you? Were you expecting these changes or anything that popped up that said, "Oh, I wasn't thinking this was going to be my experience after being treated?"

Rachael Kearney: I did surprise myself at how well, relatively speaking, I coped with the puree diet. I think I thought that was going to affect my mood. The weird thing about my journey that I've shared with Call On Courage and just my story in general is I had 3 difficult years all truncated together. So before I got my esophagus cancer diagnosis, I've had burnout because I've been part of a startup that was a bit bonkers and been working excessive hours and stuff like that. So because I've gone from burnout to then going into this physical illness, from mental health to physical illness, and then coming out the other side of that, I was thinking, "Is this going to really be a setback in terms of mental health journey?" And amazingly, it wasn't. And I think there was things that had been put in place in my life from the burnout that was like support networks and things-- I'm very creative, so things creatively speaking that I put into my lifestyle that I thought just really bolstered my mental health and kind of allowed me to recognize there was a purpose in this quite messy journey. Obviously, the surprise was, "Oh my gosh, I'm living off soup a lot and blended curries and things like that and everything." My blender gets used all the time, but I've also been quite determined to try and not hibernate or not massively change my social life. I've had to adapt my social life. And in the past, it would be a 3-course meal and a bottle of wine. Wouldn't think anything of it. But these days, it's just literally 1 course. It's either pudding or something savory that someone's blended if I can go out and get that, and then 1 glass of alcohol, and then I'm full.

And I'm having to get in the habit of eating little and often. And I don't experience hunger. That's another sort of side effect. There's weird things about it because I don't experience hunger. It has become quite liberating because I've not got food on the brain. I'm not thinking about my next meal or-- I recognize the old version of Rachael was having to work a busy job, and then there was a lot of preparation around food and cooking from scratch and going to the shops and all of that kind of stuff. And everything's so much more simplified now in terms of what I purchase, whether it's ingredients or premade stuff. And it's quicker, and I'm literally just getting the nutrition in. There's still a pleasure to eating certain types of food, but that emotional connection to food has totally gone. And just the hunger isn't there. I've probably got to be a little bit more careful because I get a lot of steps in in a day because I'm active, that I should take snacks with me just because, even not having hunger, suddenly, I can be a bit-- not dizzy but light-headed. And that's when I recognize my blood sugar's low, and I need to kind of get something in to kind of give me energy. But yeah, the surprise would be, I guess, how liberating not having hunger is. And it's one less thing to think about, even though people listening to this, if you love food, that will be hard to wrap your head around because I understand that because I think it's such a big part of our social life and how we express ourselves.

Dr. Frank Penedo: Rachael, I mean, it sounds like you've been coping remarkably well. And I think it's not-- shouldn't be very surprising to all of us that most cancer patients actually do very well. It's a normal fear, concern, anxiety surrounding the diagnosis and treatment. But most of them adjust really well, making these changes and adaptations as needed so that they can manage treatment-related challenges, limitations that are going to persist over time. Anything that you would advise for cancer survivors and patients on coping with cancer?

Rachael Kearney: My 2 big things, I would say, that change stuff is community and purpose. And I think it's an obvious thing to say, but it's not going into that sort of tunnel mental health-wise around like, "Why me?" Because cancer is so indiscriminate, and the statistics we see on TV in the UK is 1 in 2 of us will have cancer at some point in our lifetime. It's obviously just more of a surprise when it happens when you're younger. But I'm massively grateful because there's a very special treatment center in the UK called the Christie, so that's where you go and have chemotherapy. And I was sat in the waiting room one time in the Christie, and there was just a very smartly dressed gentleman probably in his 70s. And I was asking which doctor he was waiting to see, and it was the same one as mine. And it turned out that he had exactly the same cancer as me. But when we spoke about what his treatment was, he was told he had about 6 weeks to live. Esophagus cancer is an aggressive cancer and I'm just-- honestly, there's not a day that goes by that I don't give thanks because the gratitude side of things is it was actually treatable even though it was advanced, and they were able to remove it. So I'm hugely thankful for that. And I know there's going to be people listening to this at all different stages of their cancer journey and different outcomes, but I think the community side of things for me was actually having friends that were like family that kind of swept in in Manchester that would come and visit me. I mean, come and visit me when my hair was falling out, when I was looking a mess. It was sort of important that people saw me at all different stages when I had the feeding tube in and post-surgery and stuff like that. But, yeah, I was massively grateful for that community.

So I think being part of some kind of community or being open with friends around where you are and what you need-- and sometimes, you need privacy as well as that. But yeah, I think connecting with people and seeing people when you're unwell is important to process stuff with people.

Dr. Frank Penedo: Absolutely. You touch on so many words that resonate with me as a behavioral scientist. We know social support and community is just critical to helping individuals navigate through a cancer diagnosis and survivorship. Social support is one of the strongest predictors of quality of life, for example. So having that sense of community support is really critical, and it sounds like you had that available for you. Also, having faith in the treatment you're getting and your treatment team is critically important because that's going to empower you to understand and believe that you're going to be able to challenge this and fight it and get better. You talked also about sense of purpose and sense of purpose and gratitude. And sense of purpose is really important. And I want to talk a little bit about this website and podcast, Call On Courage, which I love the name. So we know that cancer can be a devastating experience to many, and having courage is really a word that I use to describe many of the cancer patients and survivors that I work with, that I interact with. Can you tell us a little bit about this Call On Courage project and what your goals were?

Rachael Kearney: Yeah. Oh, absolutely. It's been something-- I actually started it prior to having cancer. So I started Call On Courage and the website CallOnCourage.com that started when I had burnout because I was really-- I've been basically part of something, a business venture that was faith-based. And I kind of thought that was something I was going to be part of for years and kind of do it with excellence and really go for it. And so when I did have burnout, it was just devastating to really let go of that because, yeah, I thought that was part of kind of what my future career would be attached to. So Call On Courage started initially just as a blog. I was just writing to kind of process some of those feelings and work through some of the sort of things that I felt. It sounds like a strong word because it was a work venture, but a sense of grief, a sense of loss to do with not being able to sustain in the business. So writing and blogging was just something that helped me navigate those feelings. And then I just recognized I ended up-- if I'm honest with you, I deleted a lot of those posts because I guess they felt like quite journal-like in their quality. And I thought, you know what? I want to create something that's a platform and a conversation starter about other people. There's so many other people out there that have got stories about having to start over or they've tried something, they failed, it's not gone in the way that they thought it would go. And so creating Call On Courage as a podcast, doing it as a podcast has definitely opened the door for just building friendships and connections across the world, basically with all different types of people that have done interesting things.

There's a woman that I'm still in regular contact with based in California. She knew at elementary school that she wanted to be a software engineer. She achieved that and then decided she hated it and then ended up having to do something totally different. There's another woman, Lu in LuLand, who's all about growing old outrageously. And she was in Portland and wore lots of fabulous outfits. And then she's moved to South London. And she's in touch with me now regularly as well. And, yeah, having a conversation with a guy, Mike Janda, who had a creative agency that serviced Hollywood and did $25 million worth of billings to creative clients. And we're having a conversation this afternoon. So I've not got a massive Instagram following or anything like that, but it's something very emotive about courage. And I think we've all got-- everyone's got some kind of story about grit and stamina and having to kind of dig deep to make harder things happen, whether that's health or career or whatever it is. But I'm particularly interested in that connection between creativity and courage together.

Dr. Frank Penedo: It is so important for other patients and survivors to hear a story from a survivor like yourself. It's relatable. It creates a sense of commonality, understanding that they're not alone and relating to experiences that you've faced, even if they have a different type of cancer, because some of these challenges are very universal across different cancers. And let me again thank you for sharing your personal story, which is very powerful. How do you think hearing your story can help someone cope with a challenge like a cancer diagnosis?

Rachael Kearney: Hearing my story?

Dr. Frank Penedo: Yeah, your personal story.

Rachael Kearney: I mean, my type of cancer is rare. So I was finding when I was googling-- I mean, it's not the best thing to do when you instantly get a diagnosis, but I was googling esophageal cancer. And the stats around it on Google aren't great. Yeah. It wasn't great when I was unwell to look at that, but it took a long time to get to actual sort of stories or testimonials around how people recovered from esophagus cancer. And so I felt a bit like one of the reasons-- and this is why I've written a piece for Cancer.Net as well. It was important to write about my story, was that at least there's a few more websites that have featured kind of what I talk about is my journey, what's been positive about recovering from esophagus cancer, because I was really struggling to find those particular stories online. And it was skewed-- well, the data around esophagus cancer is skewed way more towards much older people over 65, heavy smokers, drinkers, and more men that have this illness. But I mean, I also want to give sort of grace for the fact that every type of cancer is different, and even just speaking to people that have had breast cancer or ovarian cancer or whatever that is, or even a benign tumor that might have grown somewhere else, it's so case-by-case specific that I wouldn't be in a position kind of to dish out advice to say, "Oh, everything is going to be fine once you get your diagnosis. And it's about do these 3 steps towards gratitude and a creative project and X, and everything's going to be peachy." I really wouldn't patronize people with that information because I think you have good days and you have bad days with it. And it is definitely a journey of processing it through. I think me personally, I found my faith in my prior life really kind of bolstered things as well when I was processing things on my own that I wasn't kind of totally alone in working that stuff through. But I just think, yeah, kind of going back to the original point, I think it was just really practically important to kind of get a bit more content out there about esophagus cancer that's coming from a younger perspective and from a female perspective, because I think that was something that I found hard to research on when I was looking.

Dr. Frank Penedo: It's certainly a challenge, Rachael, for many providers, because there's a lot of resources for breast cancer, for example, prostate cancer, but the less common, more rare cancers, we still haven't done a great job of getting the word out there and creating the necessary support services. So I cannot over-emphasize how important it is to hear a personal story like yours to help these survivors. Just a few words in closing, Rachael, what advice do you-- what advice do you have for other people with cancer and survivors who are interested in sharing their story?

Rachael Kearney: Yeah, I think even just writing down what's happened for yourself is really critical. I think you don't have to necessarily get your story out on a blog. I was nowhere near that headspace as I was going through my treatment or illness or anything like that. But writing definitely kind of helped me process some of those feelings and the difficulty of it. I think if you're in a position to be able to-- I mean, I'm quite fortunate that I come from that background of building websites and creating stuff for myself, and I'm quite used to doing that. But I think if you can do it through a free platform or on social media and start to share your story when you're well, that's also a really great way of getting it out. But I've been really surprised and fortunate that I've approached places like Cancer.Net and, in the UK, Macmillan and some other cancer charities and cancer blogs and just asked, "Would you be interested in publishing my story?" And that's led to some great conversations like I'm potentially doing some press for another digestion charity in the UK that wants to talk about Christmas and the difficulties of someone like me living on a puree diet, kind of how you navigate holiday season or whatever with food.

So I've just found it's been a source of conversation starter and a sense of-- I'm in this interim phase between recovery, and I want to get back into work and stuff like that. And it's enabled me to kind of create things and pieces of work that I'm proud of. I'm in creative industries, so I can talk about that when I'm in job interviews and things like that as well. It kind of feeds into that, which has been wonderful. But I think you're in charge of your own story, and you don't have to overshare anything. So share as little or as much as you want about it. But I've definitely found there has been a response to it and, because I've shared with much bigger cancer organizations, that's also, on a very pragmatic level, that's increased a lot of traffic to CallOnCourage.com, and I'm seeing a lot more visitors from around the world. And the spread is kind of mixed a lot more. So I'm massively thankful for that because it's just wonderful that other people's stories are kind of getting out there as well through the blog.

Dr. Frank Penedo: Well, Rachael, I want to thank you for sharing your very remarkable and inspiring story with us today. Thank you for your time, and it was great having you.

Rachael Kearney: Oh, thank you so much, Frank. I've really enjoyed it.

ASCO: Thank you, Ms. Kearney and Dr. Penedo. You can find more stories from people with cancer at the Cancer.Net Blog, at www.cancer.net/blog.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

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Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

The 2019 World Conference on Lung Cancer was held September 7 to 10 in Barcelona, Spain. In this podcast, Dr. Vamsidhar Velcheti will discuss a study presented at this meeting that looked at the effects of a new drug targeting a specific genetic change, or mutation, in some people with non-small cell lung cancer.

Dr. Velcheti is Associate Professor and Director of Thoracic Medical Oncology at NYU Langone’s Perlmutter Cancer Center. He is a member of the Cancer.Net Editorial Board and is also the recipient of a 2012 Young Investigator Award and a 2015 Career Development Award from Conquer Cancer, the ASCO Foundation. Dr. Velcheti has no relationships to disclose related to this drug.

ASCO would like to thank Dr. Velcheti for discussing this topic.

Dr. Velcheti: Hi. This is Vamsi Velcheti. I'm the director for the Thoracic Medical Oncology Program at NYU Langone Hospital. And it's my pleasure to discuss an abstract presented at the World Lung Cancer Conference in 2019 in Barcelona. And the abstract I'd like to discuss is treatment with Amgen 510, Amgen five, one, zero, which is a highly selective potent KRAS G12C inhibitor. This was the data presented by Dr.  Ramaswamy Govindan at the World Lung Cancer Conference in Barcelona in 2019.

So KRAS G12C appear as mutations in lung cancer are the most common driver oncogenic mutations. And, in fact, KRAS G12C was one of the first driver oncogenic mutations that was identified in non-small cell lung cancer. However, despite our several efforts to target KRAS G12C with multiple different drugs, we have failed to develop an effective targeted therapy option for patients with KRAS mutations. And this is very much unlike other mutations like EGFR, ELK, ROS, RET. So these mutations have a lot of treatment options for patients with targeted therapy. But unfortunately, that's not the case for KRAS mutation positive lung cancer patients. And KRAS G12C inhibitors like for Amgen 510 have showed us a way forward in terms of developing more effective targeted therapy treatments.

So this abstract presented by Dr. Ramaswamy Govindan at World Lung Cancer Conference is a fierce one, the trial of AMG 510. And in this study, they enrolled all types of solid tumors and predominantly colorectal cancer and lung cancer patients with a specific subtype of KRAS mutations called KRAS G12C. That is a KRAS mutation in the code on G12C. And in this study, they have seen very promising activity, anti-tumor activity in patients with non-small cell lung cancer, especially harboring KRAS G12C mutations. So out of the 76 patients that are enrolled in the study, 34 patients were patients with non-small cell lung cancer harboring KRAS G12C mutations. And out of these 34 patients, there were patients treated in the dose escalation part of the phase I study, meaning they were evaluating the safety of the drug at low doses, and they were escalating the dose in the patient. And there were 15 patients in the study that were treated at the maximum dose that was planned. For the study, which was the 960 milligram dose. So out of our 34 patients that were enrolled in the study, 34 patients with non-small cell lung cancer, most of the patients were heavily pretreated with at least 2 lines of prior treatments. And they were refractory to prior treatments.

So after 34 patients treated with AMG 510, nearly half of the patients had a partial response to treatment. And this is a significant advancement in terms of targeted therapy for KRAS mutant lung cancers. In previous studies with other agents, we have not seen such dramatic responses. And a majority of these responses have been confirmed responses. And the study is very early, and the data presented so far was only from the phase I trial. And there are more patients being enrolled in the ongoing phase II trial with the Amgen 510 in patients with KRAS G12C mutations. And most importantly, this drug seems to be fairly well tolerated and with relatively few treatment-related adverse events. And most of the adverse events were like a grade 1 and 1, with the most common adverse events being diarrhea, nausea, and 1 case of anemia, but has a substantially better safety profile than most other chemotherapy options for patients. So this is a very encouraging study. And we are all looking forward to more of these drugs targeting KRAS G12C and certainly excited to see these early results. And hopefully we'll see more further validation of these exciting early findings in subsequent phase II trials. Thank you very much.

ASCO: Thank you, Dr. Velcheti. Learn more about lung cancer at www.cancer.net/lung. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network, a collection of 9 programs covering a range of educational and scientific content offering insight into the world of cancer care. We’re interested in your opinions about your preferred podcast format and content offerings, so we hope you’ll take a few minutes to take our listener survey. Visit podcast.asco.org to find a link to the survey and help shape the future of the ASCO Podcast Network.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Every year, the ASCO Annual Meeting brings together attendees from around the globe to learn about the latest research in the treatment and care of people with cancer. This year, attendees from 138 countries worldwide gathered virtually for the ASCO20 Virtual Scientific Program, held Friday, May 29 through Sunday, May 31.

In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, “What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?” In this episode, 3 editors discuss new research in the fields of breast cancer, sarcoma, and palliative and supportive care.

First, Dr. Norah Lynn Henry will discuss 3 studies that exploring treatment options for different types of breast cancer. Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the Cancer.Net Associate Editor for Breast Cancer.

View Dr. Henry’s disclosures at Cancer.Net.

Dr. Henry: I'm Dr. Lynn Henry, one of the breast cancer experts from the Rogel Cancer Center at the University of Michigan. I would like to share with you a few of the research highlights related to breast cancer from the ASCO 2020 Virtual Scientific Program. I do not have any relationships to disclose related to any of these studies. There were many exciting trials presented at this conference for all types of breast cancer. Today I will highlight 3 key studies that will likely change how we treat patients with breast cancer. Before I start talking about the trials themselves, I'm going to give a very brief overview of the types of breast cancer. Then I will talk about an important study that looked at the use of surgery and radiation in patients whose cancer is metastatic or has already spread to other sites of the body at the time they are diagnosed with breast cancer. Then I will highlight some research that was presented on triple negative and HER2-positive metastatic breast cancer.

As a brief review, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor positive or estrogen receptor positive and are stimulated to grow by estrogen. We treat those cancers with anti-estrogen treatments to block estrogen or to lower estrogen levels. Other breast cancers are called HER2-positive. These are often more aggressive cancers, but because they have extra copies of the HER2 receptor, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have any hormone receptors or HER2 receptors. These are called triple-negative breast cancer and are also often very aggressive cancers.

The first clinical trial I'm going to discuss was a relatively large trial conducted by the ECOG-ACRIN cooperative group. Of patients newly diagnosed with breast cancer, about 6% are actually found to have cancer in other sites in their body such as in the bone, liver, or lung, as well as in the breast. This is called de novo metastatic breast cancer. The goal of this trial was to determine whether patients in this situation should have surgery and radiation to treat the cancer in their breast in addition to drug treatment, or whether they should just have drug treatment for their cancer. In this trial, patients with de novo metastatic breast cancer of any type were treated with appropriate drug therapy for 4 to 8 months. The approximately 250 patients whose cancers improved with treatment were randomized to either have breast surgery and, if appropriate, radiation therapy, and then resume drug therapy or to just continue drug therapy the entire time. Overall, there was no difference in how long patients survived whether they had removal of the breast mass or not. In addition, the quality of life in the 2 groups of patients also appeared to be similar. These results confirm studies that have been conducted in other countries around the world and importantly examined whether surgery is appropriate in patients who are treated with modern therapies. It appears that surgery is not needed in most patients. This is important information for patients with de novo metastatic breast cancer who are trying to decide whether or not to have breast surgery as part of their treatment.

The next trial is called KEYNOTE-355 and examined the use of an immunotherapy drug pembrolizumab, also called Keytruda, in patients with triple-negative metastatic breast cancer. Immunotherapy is a treatment type that allows a patient's own immune system to help treat her cancer. We already have the FDA approved option of using a similar immunotherapy medication called atezolizumab, also called Tecentriq, in combination with a specific chemotherapy drug for patients whose cancer express PDL1. In this new KEYNOTE trial, pembrolizumab was combined with 1 of 3 possible chemotherapy options in patients with previously untreated metastatic triple-negative breast cancer. In this trial, in patients whose tumors had an increased amount of PDL1 on the cells and in the surrounding tissue, the addition of pembrolizumab to chemotherapy made it less likely for the cancer to progress compared to chemotherapy alone. Although this treatment combination is not yet FDA approved, all the drugs that were tested are already approved for use in other situations. These results are exciting because they will likely lead to new treatment options for patients with this type of breast cancer which can be quite challenging to treat.

Finally, I will highlight new results from the clinical trial called HER2CLIMB. This is a large phase 3 trial examining a new drug called tucatinib that is a pill that is designed to turn off the HER2 receptor. Patients who enrolled on this trial had previously been treated with multiple different treatments for HER2-positive metastatic breast cancer. All enrolled patients were treated with the anti-HER2 antibody drug trastuzumab, also called Herceptin, as well as a chemotherapy drug called capecitabine or Xeloda. In addition, two-thirds received the new drug tucatinib and one-third receive placebo. We learned about 6 months ago that this drug combination was pretty well tolerated by patients. And what is exciting about this trial is the patients who were treated with tucatinib had a longer time until their cancer progressed and lived longer compared to those who took placebo. As a result of this trial, the drug was approved by the U.S. Food and Drug Administration in spring 2020.

Because of the type of drug that it is, tucatinib is thought to treat cancer both outside and inside of the brain. This is important because many patients with HER2-positive breast cancer have the cancer spread to their brain. In fact, almost half of the patients enrolled in the trial had a history of metastases in the brain and many had active growing cancer in their brain at the time of trial enrollment. Importantly those patients with cancer in their brain obtained a similar benefit from the drug compared to those who didn't. Over half of patients with active cancer in their brain had at least a partial shrinkage of the cancer in their brain as seen on brain MRI when treated with tucatinib in addition to the other drugs, which demonstrates that tucatinib can get into the brain to treat the cancer. On average, patients with active cancer in their brain were more likely to live an average of 8 months longer as a result of taking tucatinib. This represents an exciting new treatment option for patients with HER2-positive breast cancer whose cancer has spread to their brain, and importantly this treatment is already available for patients.

Overall, there's a lot of exciting research going on across all the different subsets of breast cancer. As you can see, the results of these and many other important clinical trials were reported at the recent ASCO Annual Meeting and there are many more clinical trials ongoing that will hopefully result in the approval of multiple new effective treatments for breast cancer. In addition, there's research going on that is examining the impact of treatment on patients with breast cancer and trying to improve the lives of those living with breast cancer. Clinical trials are critical to the development of these new treatments.

Well, that's it for this quick summary of this important research from the ASCO 2020 Virtual Scientific Meeting. Overall, we continue on a fast track in breast cancer with many new and exciting therapies being actively studied and research helping support our patients do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming cancer conferences. Thank you very much.

ASCO:Thank you, Dr. Henry.

Next, Dr. Vicki Keedy will discuss an international study that compared different treatment options for Ewing sarcoma, as well as new research in using immunotherapy to treat sarcomas. Dr. Keedy is an Assistant Professor of Medicine in the Division of Hematology/Oncology and the Clinical Director of the Sarcoma Program at the Vanderbilt-Ingram Cancer Center at Vanderbilt University Medical Center. She is also the Cancer.Net Associate Editor for Sarcoma.

View Dr. Keedy’s disclosures at Cancer.Net.

Dr. Keedy: Hello, my name is Vicki Keedy, and I am the clinical director for Sarcoma at the Vanderbilt-Ingram Cancer Center at Vanderbilt University Medical Center. I am pleased to discuss with you some of the exciting research findings in the management of patients with sarcomas presented at this year's ASCO Annual Meeting. I have no direct conflict of interest, but my institution does participate in some of the trials using some of the immunotherapy agents discussed below. Sarcomas are a class of cancers made of many different types of connective tissue tumors. Thus, there is significant variety in the types of abstracts presented, making narrowing them down a difficult task. First, I will discuss a study that establishes the standard first-line treatment for patients with Ewing sarcoma. And then, I will finish by summarizing a few abstracts on the use of immunotherapy in various sarcomas.

Ewing sarcoma is a type of sarcoma that can start in either the bones or soft tissue, tends to occur in children and younger adults, but can present at any age. It is characterized by small, round blue cells and is considered sensitive to chemotherapy. Regimens using multiple chemotherapy agents are considered the standard first-line treatment. However, there's variation in the exact regimen with considerable differences between the treatments most commonly used in the United States versus that used in many European sarcoma centers. EURO EWING 2012, presented by Dr. Bernadette Brennan compared these 2 most common regimens to determine whether 1 is better in regards to improving survival but also to evaluate differences in toxicity. In this trial, 640 patients in 10 different European countries with newly-diagnosed localized or metastatic Ewing sarcoma were randomized to receive either the regimen called VIDE, most commonly used in Europe, or the regimen called interval-compressed VDC/IE, most commonly used in the United States.

VIDE consists of four drugs - vincristine, ifosfamide, doxorubicin, and etoposide - given together every 3 weeks prior to surgery. This is then followed by additional chemotherapy of a similar regimen post-surgery. VDC/IE consists of 2 different regimens alternating an every 2-week cycle. These are vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide, and these are received both before and after surgery. The results of this study showed an improved survival for patients who received VDC/IE that was both clinically and statistically significant. Its benefits seem to hold true for patients with both localized and metastatic disease regardless of age. Additionally, VDC/IE appeared to be less toxic with fewer episodes of neutropenic fever and fewer severe treatment-related toxic events, while also allowing patients to complete their treatment approximately 3 months earlier than patients receiving the VIDE regimen. This study demonstrates the importance of cytotoxic chemotherapy for patients with Ewing sarcoma and establishes interval-compressed VDC/IE as the standard of care.

Moving on to the next topic of immunotherapy and sarcoma, many of the abstracts presented this year related to use of those concepts in patients with various types of sarcoma. Due to the biology of sarcoma, the immune system is generally not able to recognize and attack sarcoma cells. Thus, this approach by itself has not shown much benefit in most sarcomas. However, as I mentioned, there are many types of sarcomas, and they do not all behave the same. We have seen signals of benefits in certain subtypes. Many of the abstracts presented this year evaluated immunotherapy in some of these specific subtypes or attempted to use it in combination with other treatments such as chemotherapy or radiation. Unfortunately, these studies were relatively small or did not compare the immunotherapy to a standard treatment, making it very difficult to make definitive statements about the results. But they do give us more insights into which types of sarcomas might benefit from this approach. These abstracts confirmed responses in undifferentiated pleomorphic sarcoma, synovial sarcoma, alveolar soft part sarcoma, in angiosarcoma, and Kaposi's sarcoma. There's still much work to be done to determine whether an immunotherapy approach is better than already approved treatments for these types of sarcomas, and it is essential to validate these results by treating patients with immunotherapy agents in the context of the clinical trial. I thank you for your time and hope you found this discussion helpful. I look forward to discussing more exciting results next year.

ASCO:Thank you, Dr. Keedy.

Next, Dr. Kavitha Ramchandran will discuss several aspects of research in supportive and palliative care that was presented at ASCO20. This type of care focuses on managing the symptoms and side effects of cancer and its treatment. It also includes support to help reduce the financial, emotional, and social effects of cancer.

Dr. Ramchandran is the Clinical Associate Professor of Medicine in the Division of Oncology at Stanford University, and the Medical Director of Palliative Medicine at the Stanford Cancer Institute. She is also the Cancer.Net Associate Editor for Palliative Care.

View Dr. Ramchandran’s disclosures at Cancer.Net.

Dr. Ramchandran: Hi. It's wonderful to be here with you all today. My name is Kavitha Ramchandran, and I'm a clinical associate professor at Stanford University in oncology and palliative medicine and also have the pleasure of being the Associate Editor for Palliative Care on ASCO's patient education website, Cancer.Net. And I do not have any conflicts of interest to disclose related to the research that we'll be discussing today.

ASCO 2020 was a wonderful year in terms of palliative care education and research, and I am excited to share some of the highlights from that meeting with you all. We'll be talking about a few key research studies, and we'll be discussing a couple of different things. One, what are some of the novel approaches to symptom management in palliative care? Two, how do we actually assess risk in terms of our patients and how can we better stratify patients in terms of what type of treatments are best for them, and are there novel tools we can use? Three, how can we improve care by integrating palliative care early and often, both through a primary palliative care approach as well as a specialist palliative care approach? With that, let's go ahead and get started.

So in terms of symptoms, we had a really great discussion by Dr. Roeland from Mass General on several abstracts. The couple of abstracts that we're going to focus on here, one looked at armodafinil, which is a stimulant that has been often used for cancer fatigue. And the second was looking at cannabis compounds that have been thought about in thinking about nausea and folks who are suffering from nausea due to chemotherapy.

So our investigators that looked at armodafinil looked at armodafinil in patients who had glioma, and they wanted to see that if they used armodafinil in these patients, whether or not they would have an improvement in their fatigue. Now in the past, we know that there have been a number of studies that have looked at different types of treatments for fatigue, everything from steroids, to stimulants, to herbs, and what we found is that, consistently, stimulants have not been shown to improve fatigue. The things that have been shown to improve fatigue in small studies include steroids as well as American ginseng. Unfortunately, this was yet another negative study, and what we see here is that armodafinil did not improve fatigue and in fact, at the dose of 250 milligrams, might have increased insomnia or trouble sleeping. And so with that, I think we would make the assumption that we probably need to rethink our approach with stimulants in cancer-related fatigue and, for the majority of our patients, would make the decision that stimulants may not be the best course to improve fatigue.

On a positive note, we did look at patients who were receiving chemotherapy, and, in an Australian study, what they looked at was whether the addition of a THC plus CBD compound - now, this was both THC and CBD 1-to-1 - could improve nausea. And what they found is that, for these patients who all received the normal prophylaxis-- so they got Zofran. They got a D2 receptor antagonist, such as Compazine. If you added the THC-CBD compound, those patients actually had better nausea control, which was fantastic. However, they did also have some side effects from the THC-CBD, including dizziness, sedation, and disorientation. Yet despite these side effects, the patients really felt better, and so they were likely to continue using the cannabis. And they would actually choose to continue using the cannabis.

Moving on to a different note, there were a variety of different studies that looked at risk assessment, and can we actually identify which patients would benefit most from which intervention? And there was a couple of different types of studies here. One looked at the utilization of patient-reported outcomes to see whether or not we can identify patients who may be at more at risk for poor outcomes. We know Ethan Basch published, a couple years ago, a landmark study that showed that if you integrated patient reported outcomes, also known as PROs, routinely into cancer care, you could improve survival. So basically, if you looked at symptoms, evaluated those symptoms, and treated those symptoms early and often, people lived longer and lived better.

Now, can we use this data that patients give us through questionnaires on a regular basis, can we use this data in other ways? And we actually had a few studies here that looked at patients who had metastatic disease. And Dr. Batra et al. from Calgary looked at 1,300-plus patients, and what they found was that patients who had fewer symptoms tended to do better. And it seems like a kind of obvious point. If you have more symptoms, you might do worse, but I think the routine assessment of symptoms in patients and utilizing those symptoms is not done. So if we know that patients who have fewer symptoms might do better, may be able to use that data to see whether or not those patients might need more support or to use that data to see if those patients may not be the best patients for a clinical trial. Maybe we need to do symptom control first. So it does help us to risk-stratify and understand that patients that have more symptoms tend to have a shorter survival. Patients that have fewer symptoms tend to have a better survival.

Additionally, we have some really interesting data from Dr. Supriya Mohile at the University of Rochester looking at the use of a different type of assessment called the geriatric assessment for patients who are older. Now, we know that the geriatric assessment can identify patients who are at high risk for things like falls or cognitive changes or dementia, but what we don't necessarily know is whether if we routinely use the geriatric assessment, it helps us with our cancer treatment. And what they did in the study is they actually randomized patients to do the geriatric assessment. And in 1 arm, they showed the geriatric assessment to the oncologist, and in the other arm, they did not. And what they found is when they showed the geriatric assessment to the oncologist, the patient actually received treatment that was probably better for them based on the findings of their geriatric assessment. So patients who were more frail or who had more findings that would require an assessment and treatment had those things done. So if they needed a fall assessment, that got done. If they needed some neuropsych testing for their dementia, that got done. And for those patients, the oncologist often would choose to give a slightly lower dose of treatment to prevent further adverse effects. So what they found is that if you did a geriatric assessment routinely for older patients, you could appropriately provide for those needs and actually give them the treatment that is correct for them, preventing adverse events, preventing higher-grade toxicities, and ensuring that those patients got the best care.

And then finally, coming to our last group of trials, we had a really great discussion from Amber Barnato from the Dartmouth Research Institute. So it looked at variety of clinical trials of early palliative care integration as well as integrating palliative care through primary palliative care intervention. Now, what's the difference here? So primary palliative care intervention is when you teach clinicians, like your oncologist, to do palliative care themselves. So that's when they prescribe an opioid for pain, or that's when they do a goals of care discussion as part of routine advance care planning. Now, specialist palliative care interventions look a little different, and that's often when you have someone who's board-certified in palliative care and hospice, and they come in and do another consultation. And this would be akin to having a cardiologist come help your primary care doctor take care of your hypertension. This would be pulling in another team. So that's the difference between primary and specialist palliative care. So what we saw here is that there were 2 different types of interventions that were both really interesting.

Now 1 was done in University of Pennsylvania, where they actually looked at several thousands of patients who had their oncologists get a little nudge through an email that said, "You know what? Your patients coming in this week might be at a little bit of a higher risk for a poor outcome, at a higher risk for mortality. And when that happens, it might be good to do some advance care planning." So that these oncologists that got this email nudge, they were more likely to do the right thing by their patients. They were more likely to do an advance directive, and they were more likely to ensure that these patients had their goals of care documented and their prognosis documents within their charts. So something as simple as a mortality prediction done through a computational tool and an email to those oncologists could really improve getting the basics done for patients, such as getting their advance directive done.

Additionally, when we think about, now, specialist palliative care intervention, Dr. Barnato actually made a really beautiful point. She actually looked at a couple of different studies, 1 done by Tom Smith looking at integrating palliative care in phase 1 populations and the other by Dr. Areej El-Jawahri looking at integrating palliative care into the acute leukemia patient population. And both of these studies were really excellent studies that showed quality of life improvement with early integration of palliative care. And that is fantastic, and it supports the work that was led by Jennifer Temel in 2010, where she saw that if you integrated palliative care early and often, those patients had better quality of life, those caregivers did better, and those patients live longer.

And these studies continue to support the fact that early integration of palliative care improves quality of life for patients from a variety of different walks, whether it's phase 1 or acute leukemia. But what Amber Barnato pointed out was that palliative care also does something really different. What palliative care does is it also improves the way that we communicate across systems, and what she said, and I think it's important to point out, is that we don't often account for that in our metrics. We don't often point out that when a palliative care doctor talks to an oncologist, it decreases the anxiety of the oncologist. It makes the oncologist deliver better care. It actually changes the infrastructure of how we deliver care in the system, and that improves quality in ways that goes beyond the biopsychosocial model of just quality of life for patients but really changes the paradigm of how we deliver care across the system. And that we not only need to measure quality of life for patients but really look at some of these system changes that palliative care really helps to propagate and think about how that could be measured ongoing.

So it's been another great year for research. We're really excited about what our colleagues are doing out there in palliative care and supportive care and both in improving systems, improving risk assessments, and improving symptoms. We look forward to another year of research in ASCO 2021. Thank you so much for having me here today to talk to you a little bit about what we learned from our colleagues and friends.

ASCO: Thank you, Dr. Ramchandran. Learn more about the research presented at the ASCO20 Virtual Scientific Program at www.cancer.net/blog, and subscribe to Cancer.Net podcasts on Apple Podcasts or Google Play for additional episodes in the Research Round Up series, released throughout the summer.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. 

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Dr. Allison Kurian and genetic counselor Kristen Mahoney Shannon talk about what people should know about genetic testing and hereditary breast cancer, including what to expect when meeting with a genetic counselor, ways to reduce your risk of developing cancer, and talking about genetic test results with family.

 Dr. Kurian is a Professor of Medicine and of Epidemiology and Population Health at Stanford University School of Medicine, and Director of the Stanford Women’s Clinical Cancer Genetics Program. She is also the 2023 Cancer.Net Specialty Editor for Breast Cancer.

Ms. Shannon is a senior genetic counselor and Director of the Cancer Center Genetics Program and Director of Genetic Counseling for the Massachusetts General Hospital Department of Medicine. She is also a 2023 Cancer.Net Advisory Panelist.

View disclosures for Dr. Kurian and Ms. Shannon at Cancer.Net.

Dr. Allison Kurian: I'm Allison Kurian. I am a professor of medicine, oncology, and epidemiology and population health at Stanford University. And I am speaking today with my colleague, Kristen Shannon, who will introduce herself.

Kristen Shannon: Hi, it's great to be here. My name is Kristen Shannon. I am a genetic counselor and the director of cancer genetics at Massachusetts General Hospital in Boston. And I have no financial relevant disclosures to report.

Dr. Allison Kurian: Thank you, and I have no relevant financial disclosures either. Very good. So today we will be talking about breast cancer and inherited risk and genetic testing. And let me start by providing a definition of a genetic or hereditary condition. So the way we think about this is something that has a high risk for developing a disease, not a certainty, but a high risk, and runs in families, generally because of a genetic finding that we can identify. And that typically is identified through sequencing, testing of blood or saliva samples, and typically allows us to find a change that we know is clearly associated with disease. A good example for breast cancer are the genes BRCA1 and BRCA2, which some may have heard of, and we will talk about further. So that is just an example, and we will get into more of the details of this as we go on. But I think the point is something that runs in families often is seen with the trait, so for BRCA1 or BRCA2, that would be breast cancer or ovarian cancer, affecting people in every generation. And having what we call for these kinds of genes an autosomal dominant inheritance pattern, so inherited from either parent. And taking only 1 copy that is not functioning to give a person higher risk of the condition. So that's sort of a bit of the basics here on genetic or hereditary risk.

And just to give a sense of how common hereditary breast cancer is, we think that in general this may account for, I would say, somewhere between 5% to perhaps 10% of cases of breast cancer. And Kristen, please jump in and tell me if you think differently. But that would be my ballpark. And I think probably the majority of those are the BRCA1 and BRCA2 genes that I mentioned, although there are others that we are recognizing are playing more of a role than we thought, and we'll discuss those, too. So let me give you a chance to continue and respond, Kristen.

Kristen Shannon: Yeah, no, I totally agree. And I was thinking that maybe I could talk a little bit about some of the features that are suggestive that there could be one of these inherited breast cancers in the family, because recognizing these signs of hereditary breast cancer can be super important for early detection and prevention of breast cancer. So first, multiple cases of breast cancer within the family, especially among close relatives like parents, siblings, children, those can be a sign that the cancer is inherited. Another important sign is early age of onset of disease. So breast cancer diagnosed at a young age, typically before the age of 50, might point towards hereditary risk. And it's not always the case, but it's something to be aware of. Also, if there is a history of ovarian cancer in the family, especially if you see it in conjunction with breast cancer cases, that's a significant sign that there could be something inherited in the family. And while it's rarer, male breast cancer can also be associated with hereditary gene mutations. So if there's a history of male breast cancer in the family, it's definitely something to think about in terms of hereditary risk.

Multiple cancer types in the family can also be another clue. It's not always just breast and ovarian cancer. If you see a family history of both breast and ovarian cancer or pancreatic cancer or prostate cancer within the same family, that also might be a sign of an inherited cancer syndrome. For individuals of Ashkenazi Jewish descent, it's worth noting that they have a higher prevalence of certain gene mutations in specific genes, specifically BRCA1 and BRCA2, which Dr. Kurian has mentioned before. So a family of history of breast or ovarian cancer in an Ashkenazi Jewish individual should be noted as a higher sign that this cancer could be due to an inherited gene. And lastly, if someone has had breast cancer in both breasts, that's called bilateral breast cancer, and that might indicate hereditary risk.

It's important, though, to remember that it's not just about any single sign in isolation. You really need to take a look at the bigger picture and the bigger context of the family. So if you notice any of these signs in your family, it's a good idea to seek guidance from a health care professional, like a genetic counselor or a medical oncologist, and they can help assess the family's risk and recommend genetic testing if needed. Dr. Kurian, did I forget anything or leave anything off?

Dr. Allison Kurian: Perfect as always. I will just add a little bit here in terms of the specific gene names that we think about, because sometimes it helps people to have sort of a list in their minds, not that we expect you to remember the whole alphabet soup of these different genes. And let me just say that I think it's always a bit of a hodgepodge, some of these names. I used to wonder how people come up with these names, and often there's a bit of a history there. But I will just go through a few of them. We now have some practice guidelines, and they are basically put together by a group of experts who review all the evidence frequently and come up with recommendations. And so there is a list in these guidelines of basically which genes we think are appropriate to test for breast cancer in families, because there's enough evidence to suggest that.

And so in addition to BRCA1 and BRCA2, the ones that I think of as the most important, and I'll want to hear Kristen's thoughts about this, too, but the ones that we see most often are called ATM. Sounds like a cash machine, unfortunately not, but ATM. CHEK2, C-H-E-K-2, and then one called PALB2, which stands for Partner and Localizer of BRCA2, and is a lot like BRCA2 in its risks.

There are some other genes that give breast cancer risks that are less common. One of them, CDH1, is a gene that also causes an increased risk of stomach cancer. There are a few others that we always keep in mind. There's one called PTEN that's very rare that causes a syndrome called Cowden syndrome that I certainly haven't seen much of. Kristen may have seen more, but it's not something we see often and goes with a lot of other features in families. There are 2 genes that I think we recognize more in recent years and like to be sure we test, called RAD51C and RAD51D, and those both give increased risks. And then another one that I always think of as important here is TP53, and that is a gene that causes something called Li-Fraumeni syndrome, which has probably the highest cancer risks of which we know. There's another one, STK11, that gives some risk, NF1. We see these as being less frequent contributors. Those are the ones that I kind of keep in mind. And again, there will not be a quiz on the alphabet soup, but just so you're aware of what kinds of names you might hear. Kristen, please jump in if I've forgotten any or anything else you want to say.

Kristen Shannon: No, I think that that's important. I think the only thing that I would add is that some people think when they go in for breast cancer genetic testing, they only are getting the BRCA1 and BRCA2 gene. And it's just important for people to realize that that's not really a complete test at this point, as you mentioned, Dr. Kurian.

Dr. Allison Kurian: Totally agree, and thank you.

Kristen Shannon: Should we move into how to prepare for a genetic counseling appointment?

Dr. Allison Kurian: Please, yes.

Kristen Shannon: Sure, okay. So preparing for a genetic counseling appointment for breast cancer risk can be helpful. First and foremost, we suggest that you gather your family health history. So reach out to your relatives and compile as much information as possible about your family's health background. Pay special attention to any instances of breast cancer and ovarian cancer, prostate cancer, pancreatic cancer in the family. And if any family members have had genetic testing, it's really helpful to jot down those test results as well and bring them with you to the appointment. The other thing is to think about your own personal medical history. You know, think about if you've had any past diagnosis, any treatments, surgeries, or medical conditions, especially those related to breast cancer, your genetic counseling appointment will include a discussion of those. The other thing is, you know, if you've had any medical tests related to cancer, it's important to gather those records if they're not already in your hospital's medical record system that you are going to.

Another good idea is to just prepare a list of questions that you might want to have answered. So what do you want to know? Are there specific concerns or specific things you're curious about? It's also important to understand what you want to get out of this genetic counseling encounter. Do you want to just clarify your risk of having a gene? Do you want to consider genetic testing? Or do you want to talk about just managing your risk for breast cancer? That's super important to have that in mind before you actually go into your appointment. Lastly, I would consider bringing along a person, a supportive person with you to the appointment. Having someone with you can help provide emotional support because sometimes these visits can get emotionally charged, but it also can help to have someone remember important details that you will discuss with your health care provider. So it's really important to just arm yourself with information, questions, and support so that the appointment is as productive and informative as it can be. Do you have anything else you'd like to add, Dr. Kurian?

Dr. Allison Kurian: It's wonderful to have your expert perspective on this. And I guess any thoughts about really what's inside the box? I think sometimes people just sort of wonder what's going to happen when I go in that room. Sometimes we have patients come in and say, “What are you guys going to do to me? Will there be surgery done?” And we reassure them that we are not doing anything that wild. And so maybe just a sense of kind of walking people through what will happen when they go to meet with genetic counselors.

Kristen Shannon: Absolutely, thanks for bringing that up. So during the initial meeting, first you'll probably discuss your personal health history, again, any past diagnoses, surgeries, medical conditions. And then typically a genetic counselor or a medical professional will dive right into your family health history. So they'll ask a whole bunch of questions about your close and extended family members to build a really comprehensive picture of your family and the cancer diagnosis in it. They'll want to know if anyone in your family has had cancer, and they'll also want to know what type of cancer that person has had and also the age at which that person was diagnosed. So those are the 3 pieces of information that your health care provider will want to get from you.

The genetic counselor will also probably ask you about what you want to get out of this encounter to make sure that you're both on the same page. Again, do you want genetic testing? You know that already. Or do you want to just talk through the process?

So the big part of the initial meeting is really education. The genetic counselor will explain what Dr. Kurian described at the very outset of this discussion, what's the genetic basis of hereditary breast cancer, including all the specific genes that Dr. Kurian—the alphabet soup that we talked about. Talk about inheritance patterns and the implications of having a genetic mutation. The genetic counselor will probably also first assess your risk of having a mutation in one of the genes, and then they'll also talk to you often about genetic testing. So if genetic testing is on the table and you and the genetic counselor both agree that it's a good step, they'll walk you through the process of informed consent. And so this ensures that you understand what the testing entails, the potential outcomes, the implications of the test results.

And then if you decide to go through with genetic testing, you will provide a blood or a saliva sample. And then it's a waiting game because these test results can take several weeks, usually about 3 to 4 weeks to get the test results back. When the test results come back, you'll typically have a follow-up appointment, either in-person or on the phone with your genetic counselor. And that's when they spend a lot of time interpreting the test results, explain what they mean for you and your health, as well as discussing the appropriate risk management strategies, if necessary. And if a gene mutation is identified, a genetic counselor will guide you on how to manage these risks. But it will depend on the specific mutation that is identified. And then the other thing that the genetic counselor can help with is just the emotional support. Some people have a harder time than others hearing this information. And also to talk about how to tell your family members about this. So in a nutshell, the initial meeting with the genetic counselor is about gathering information, assessing risk, and potentially deciding on whether or not you're going to have genetic testing. And then after that step, it's about interpreting the test results, talking about next steps, and providing emotional support.

Dr. Allison Kurian: Thank you, Kristen. That was wonderful and very complete. And as I was listening to you, first of all, I was thinking about my general admiration for genetic counselors, which is huge. They taught me everything I know about this field. But so also kind of highlighting the key things that a meeting with a genetic counselor will do for you, as you so nicely did. And I think it's getting the right test ordered, making sure that the results make sense to you, and going beyond the patient. But I think those are sort of the key aspects that you communicated really well of the things that we want to get done there.

Kristen Shannon: Well said, well said. And I couldn't agree more.

Dr. Allison Kurian: And what do you think about the family part in terms of how that gets done?

Kristen Shannon: Right, so discussing your genetic test results with family members can be hard and challenging, but it's really, really important. In terms of talking to your family members, I think first, determine the way you're going to notify your family members. So are you going to talk to them? Are you going to send them a letter or an email? And how you share the information may be different based on your relationship with that person. So for example, you may sit down over coffee with a close family member to talk about your test results, but you may choose to write a letter to someone that you don't have that much contact with.

The next thing that I think is really important is to be prepared. So before you even start to have this conversation, make sure that you have a clear understanding of your genetic test results, the implications to you and to the family member. That's super important before you even start to have the conversation so that you can explain things to people in simple terms without too much medical jargon and make sure you keep it straightforward. It's really helpful to have a copy of your genetic test results and to provide that to your relatives if you're comfortable doing so, because then they can take that information with them to their genetic counseling or genetic testing appointment, which can be incredibly essential in terms of making sure that they get the correct test at the right time and the test results are interpreted correctly.

The only other suggestion I have is just to keep in mind that family members are going to react very differently to this information. And some people will be very matter of fact about it. Some people might get a little distracted by this whole thing. So just to be patient with people and keep the conversation open. Allow them to call you if you're willing to do that so that the conversation can develop over time because, you know, really, in the end, the goal is to make sure that everyone in the family is well informed and makes decisions based on their own health and their well-being.

Dr. Allison Kurian: Thank you. I couldn't agree more. And we sometimes, as people may have heard, call this “cascade genetic testing.” So a patient is tested. Somebody who's already had cancer maybe is tested. But then we have the opportunity to have this cascade of beneficial genetic testing, where we can get to people before they have cancer and work on prevention and screening, which I'll talk about in a minute. And I will say that, in general, we here in the United States, and certainly other places as well, don't do as well as we would like with cascade testing despite all best efforts of everyone. And so just to emphasize that family notification is super important, genetic counselors are wonderful at helping people to do that. And I think also additional strategies and interventions are underway to try to help make that easier.

So if I may, I'll talk just a little bit about kind of what we do when we find something. Is that okay to do?

Kristen Shannon: That sounds great. Talk about people, you know, what they can do about their test results.

Dr. Allison Kurian: Good. Yeah, so I always think that's important. I'm an oncologist by training. I'm not a geneticist. And again, it's only thanks to the brilliance of genetic counselors like Kristen that I have learned what I have for the last 2 decades working in the field. But so I tend to think in terms of what can we do to treat this person differently if they have cancer to prevent or reduce the risk of a future cancer. And so what I would say is increasingly over the last few years for a person with breast cancer, as well as some additional cancers, it started to matter what these results are in terms of how we treat the person, whether we might give different medications. And that's really exciting because for years in this field, we didn't have that, and now we do.

And so the drugs that are increasingly important are called PARP, P-A-R-P, inhibitors. And sometimes, if a person has a BRCA1 or BRCA2 gene mutation, we might even offer those drugs to treat a breast cancer or, in other cases, ovarian, prostate, or pancreatic cancer. So I think the testing can matter like never before in terms of what we might do to take care of people's cancer. Sometimes we might also choose a different surgery. So sometimes a woman who has a diagnosis of breast cancer might choose to do a more extensive breast surgery, she might choose a double mastectomy to reduce her risk of getting a second breast cancer. That's never required. She certainly doesn't have to do so extensive a surgery if she doesn't choose, but it is an option that some people might choose. And there might also be other cancer risks to manage in somebody who had breast cancer. BRCA1 and BRCA2, for example, give a high risk of ovarian cancer. And so we might talk with someone about the possibility of removing ovaries to prevent an ovarian cancer, which often is recommended with BRCA1, BRCA2, and other such gene mutations.

I will say that I think for somebody who hasn't had cancer yet, or hopefully ever, particularly as we think about breast cancer, we're often thinking about intensive screening. So starting often earlier than a person would if she didn't have high risk and generally adding magnetic resonance imaging, MRI, to screening with mammogram alone. And that really is, I think, the cornerstone for women at high risk is adding that breast MRI screening. For pretty much all of the genes I mentioned, that would be clinically indicated and covered by insurance and important to do. MRI has no radiation, very effective at finding breast cancer early.

So I think to summarize, it's really all about understanding risk based on a particular gene mutation, understanding if a different kind of treatment is needed for the cancer that a person has, understanding if any sort of preventive measure is needed for future cancer risk, and making sure that the screening we have for breast and for other cancers is appropriate to the level of risk. Anything to add there, Kristen?

Kristen Shannon: No. No, I think that that's great.

Dr. Allison Kurian: Absolutely. Yeah, so I think it's wonderful to have this opportunity to speak about the importance of genetic testing, which is I think more important than it ever has been at this time for the care of patients with breast cancer and their families. And so as we move into breast cancer awareness month, it's great to be able to talk about this. Thanks so much.

Kristen Shannon: Thank you so much. I agree. And if you have any questions, I would suggest you reach out to your doctor or look up on the ASCO website for a referral to a genetic counselor.

ASCO: Thank you, Dr. Kurian and Ms. Shannon. Learn more about hereditary breast cancer and genetic testing at www.cancer.net/hboc.

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ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Cancer.Net Specialty Editor Dr. Petros Grivas talks to Dr. Marianne Dubard-Gault about what people with bladder cancer should know about genetics and genetic testing, including what information genetic testing can provide, how it can inform bladder cancer treatment, and what to expect when meeting with a genetic counselor.

Dr. Grivas is a medical oncologist at Seattle Cancer Care Alliance, clinical director of the Genitourinary Cancers Program, and professor at the University of Washington School of Medicine. He is also an associate member of the Clinical Research Division at Fred Hutchinson Cancer Research Center. Dr. Dubard-Gault is the medical director of the Cancer Genetics Program at Fred Hutchinson Cancer Research Center and an assistant professor at the University of Washington School of Medicine.

View disclosures for Dr. Grivas and Dr. Dubard-Gault at Cancer.Net.

Dr. Grivas: Hello, I'm Dr. Petros Grivas. I'm a medical oncologist and serving as the clinical director of the Genitourinary Cancers Program and professor at the University of Washington Fred Hutchinson Cancer Center. I'm very excited and thrilled today to discuss with one of the amazing leaders in the field of cancer genetics, Dr. Marianne Dubard-Gault, who is my colleague here at UW Fred Hutchinson and has been such a wonderful human being and advocate for her patients and also really a key opinion leader in the field of genetics and the implementation in patient care. Dr. Dubard-Gault, welcome, and I will let you introduce yourself.

Dr. Dubard-Gault: Thank you very much, Dr. Grivas, and it's a pleasure to be here. So thank you for the invitation. I am Dr. Marianne Dubard-Gault. I am a trained oncology doctor and a trained genetics doctor, and my focus now, as Dr. Grivas mentioned, is in the cancer genetics world where I help people either get genetic testing in the first place and/or their family members have interventions for their screening and early detection. I'm also an assistant professor at Fred Hutchinson Cancer Center in Seattle, Washington, and then at the University of Washington on the other side. And I lead the Cancer Genetic Survey Center at Fred Hutchinson Cancer Center. And I have no disclosures.

Dr. Grivas: Thank you so much, Marianne, and again, thank you for helping our patients. And I'm really, really excited today because it's a very important topic, not frequently discussed. And I really, really wanted to make this happen, and thanks to Cancer.Net for helping us getting the word out there. I have no relevant disclosures in this topic. My disclosures are listed on the ASCO website. And Marianne, I will start us off by asking you, just for the audience to set the stage, can you define what we call “genetics”? What exactly are we referring to?

Dr. Dubard-Gault: Yes, that's actually very important. That's probably the first thing that happens in the clinic when we talk to patients is, what is genetics anyway, right? So genetics is the study of the DNA or the genetic makeup that we all have. And that makes a person who they are, right? So looking into the genetic makeup to make sense of it and inform treatment or other interventions.

Dr. Grivas: Thank you much, Marianne. And I think it's so important again for our patients to understand the definitions here. So let me ask you, can you define the difference between a genetic mutation versus genetic alteration? How would you explain that to a patient?

Dr. Dubard-Gault: I think about them in a similar way. So, to me, a genetic mutation or alteration is a spot in your DNA. So there's a long stretch of letters, and there's a spot in there that either was copied or wasn't copied properly over. And so that leads to a command that kind of not being executed properly. And so an example of that would be if I gave you the 2 words “red” and “bed,” those 2 words would mean totally different things in your mind. And so if you were supposed to hear “red” and you heard “bed,” then downstream will be a different outcome.

Dr. Grivas: Thank you so much, Marianne. And this is very important because for the audience as you pointed out nicely, the genetic code, the DNA translates a message, alright, that becomes a protein and eventually a function of the cell. So if that code, if that message is misspelled, it can lead to different altered and changed-up protein for the cell. That has implications and can potentially predispose someone to cancer. So if we can also help the audience understanding the differences between what we call “somatic genetic mutations” and “germline mutations.”

Dr. Dubard-Gault: Absolutely. And this is also something that comes up every time because they're part of the same groups of things overall, right? So somatic means tissue or tumor. And germline, or hereditary, sometimes you'll hear that word interchangeably means inherited or hereditary or part of the genetic makeup or the code that you were born with. So different parts of our body have different genetic mutations. And that is why even with 2 identical twins, they won't have the same moles on their skin, or they won't have the same medical conditions, even if they have exactly the same genetic code. And it's exactly the same for a person who has a tumor, right? The DNA or the genetic makeup they were born with will stay exactly the same as they grow older, but the genetic makeup their tumor has as the tumor grows can change and make more or have more mutations. So testing different parts of the body will help tease out which ones of the mutations are located where? Is it in a tumor only? Is it in the genetic makeup you were born with or is it part of that transition between the 2?

Dr. Grivas: Thank you, Marianne. I think this is great when we explain to the patients what exactly mutations, alterations, means, and the difference between a somatic tumor testing, as you said, mostly to help define treatment options. And what you very nicely discussed are germline testing, looking at hereditary predisposition to cancer that can impact the patient and also family members and the broader family. And one kind of take-home message may be for our audiences, when someone is about to see an oncologist or their provider, is greatly helpful if they can do quote-unquote "their homework" and try to understand and delineate and capture as much as possible regarding the family history. And sometimes it's hard, especially when you go to distant relatives, cousins, nephew, nieces, it's more difficult, but it can help a lot and inform that discussion and whether a referral to a genetic counselor or geneticist is relevant. So that's what we try to do with nurse navigation these days to help inform people with cancer before their appointment how they can maximize to capture that information, it can be helpful to them and for the provider. And the next question, Marianne, is how common are these genetic germline mutations in people with bladder cancer?

Dr. Dubard-Gault: I think the answer is still out there. We don't have the complete answer today. We don't know all the genes that are implicated in bladder cancer today. So given that, we probably don't have the full or complete answer as to how many people with bladder cancer would have it. But kind of to get close to the answer, as close as we can possibly be today, I think it depends on the group of patients with bladder cancer that you test, but I would probably give a 1 in 10 people with bladder cancer would have an inherited genetic mutation.

Dr. Grivas: And that's very helpful Marianne. And of course, varies, of course, across the different scenarios and the family history as you mentioned, the age of cancer diagnosis. And sometimes it's interesting in patients with urothelial carcinoma, cancer in the upper urinary tract, like renal pelvis, kidney problems, or ureter, there seems to be some higher frequency of germline mutations in that as opposed to bladder cancer. Of course, it can happen in that scenario, but seems to be some higher frequency in the upper tract cases, is that right?

Dr. Dubard-Gault: I agree. Not all cancers are created equal, right? In the bladder, that's probably also true. So depending on where it starts, the type of cells that are involved, and how the person was born with certain genetic predispositions, it may very well affect how all of these are linked together in one line of event versus maybe something that happened randomly or occurred that we don't have a one specific answer or a combination of answers.

Dr. Grivas: That's a great point. And obviously, there are the huge impacts that we discussed to help prevent cancers in the bladder family. Cancer prevention mode, I call it, when I explain to the patients before they see you. And also, some patients are also asking, in addition to that family benefit in my brother’s family, is there any potential impact on the treatment selection for the bladder cancer? Any comment?

Dr. Dubard-Gault: Yes, I do believe there is actually more today than ever before, especially with the new medications that have come around, right? So sometimes a genetic mutation will happen in the DNA or the code that is important for repairing the code of the DNA, or sometimes it will happen in an area that helps boost the immune system or the response to the cancer cells by the immune system. So in that case, if we find a genetic mutation, then we can use a chemotherapy that concentrates or targets that area that's not working well and fix it, right? So that's one really important area. And then another area, and Dr. Grivas, I know you've done a lot more clinical trials and studies that involve the DNA that makes new blood vessels for feeding the tumor. And in that case, you can use a chemotherapy that would block the body from making those new blood vessels and basically shut off the feeding system to the tumors. And so that way, the genetic testing can also help the patient find a therapy that would work better for them.

Dr. Grivas: That's a great discussion. And we're doing many clinical trials to test this hypothesis. This assumption kind of practice, and we try to look at particular therapies that might be relevant in the context of a germline mutation. And those clinical trials are very promising. And I always encourage our patients to consider subsequent trials. And the other aspect of it, as you said very nicely, is that a patient who may have some changes in the code encoding some enzymes, some proteins that repair the DNA, this can cause some more mutations. And in this particular scenario, there may be a much higher response to immunotherapy. That immunotherapy may help shrink those tumors with what we call more unstable genomes. So that's very interesting to see that across tumor types, to your point. The other question is if someone is referred to genetic counseling, how can they be better prepared for their appointment?

Dr. Dubard-Gault: I think the most important thing that I would say is to really embrace it and go. Because it's often something that makes people worried that they have a genetic predisposition in the family, and they may not necessarily be ready to hear it or want to have as much information, especially being diagnosed with a cancer at the time. And so really embrace it and go for the genetic visit because it is something that could be very useful and bring information not only to you as a person for your own treatment, and/or then for your siblings or relatives for them to have access to interventions they would not have otherwise.

Dr. Grivas: What question do you think people should ask their providers? How can they better prepare for the visit with the provider overall regarding the topic we are discussing today?

Dr. Dubard-Gault: That's also very important because as much information as you can gather is really important. So, if possible, gathering as much information about your family history as you can, as Dr. Grivas mentioned. And sometimes you can't have all the information, some grandparents died, they did not share the information about their cancer diagnosis because they didn't want to upset the family. Sometimes you have no information on one side of the family because you don't know who your father's parents are, for example, or a certain relative may be OK now and they have cancer later on, and you will probably not have that information, right? We can still do the genetic test knowing that some of this information is missing. So keeping in mind that as much information as you can get is good. And if we have a lot, that's helpful, and if we don't, we will kind of factor that in our conversation. And a few other tips I would keep in mind is the timing of the testing matters. Sometimes doing the testing earlier in the process is a good thing because it takes a little while for the results to come back.

That's a sophisticated test that takes usually 3 to 4 weeks. There are many different types of genetic testing; that's also very important. You may very well have more than 1 genetic test, as Dr. Grivas mentioned. The test on the tumor, the test on your genetic makeup from a blood sample or a saliva sample. I mean, keeping in mind-- I think the third one that's really important is keeping in mind that when we do the genetic test, the results may implicate other people in the family straight away. And I'll share an example of this because this comes up in my clinic very often. So I met a brother not so long ago who had bladder cancer. No exposures, no smoking, nothing to point to a risk of bladder cancer for him, but his sister had uterine cancer earlier on before the age of 40, and then had colon cancer as a second primary cancer. And the test came back with the genetic predisposition we talked about, Lynch syndrome. And this diagnosis basically explained his cancer diagnosis on why he had an unstable genome in his tumor. And his sisters, both of his sister's cancer. So by proxy by testing him, we tested not only him, but his sister as well, even if we'll do the sisters confirmation tests, we know the sister is likely positive for this.

Dr. Grivas: Thank you so much, Marianne. The very useful information. Again, the positive impact and benefit for the broader family. What happens during and after the initial meeting with the genetic counselor or the geneticist?

Dr. Dubard-Gault: Well, I love genetic counselors, I think they're very helpful. And I work with them on a day-to-day basis. So, what they'll do is they'll sit down with you either in person or telemedicine or telehealth from the comfort of your own home or on the phone. I don't like the phone as much as I like the interpersonal connection with a person. But they'll help you draw out your family tree, put all the people in the family on the page together to kind of see and share a pattern. They'll talk a little bit more about the different types of genetic testing one person could have. And then they'll facilitate getting the genetic test that is best for you and your family. And so that really is the most important piece because they'll work with your oncology doctors and other doctors to come up with the best option.

And the one that matches the family story. And then if you're in person, you could even provide a sample, either a blood sample or a saliva sample, right there. And then the authorization and all goes through, and then the results usually will come back a few weeks later. And then the genetic counselor or myself as a genetics doctor will sit down with you when the results come back to review what they mean, not only what the actual test says, but what they mean specifically for your treatment, and/or for yourself or your screening and interventions later on, and/or your family members, if they need to be tested themselves or what needs to happen for them. And then you can obviously be referred to a specialist like Dr. Grivas or others for a colonoscopy or for thyroid ultrasound or some other tests that may be needed for these screening interventions in the future.

Dr. Grivas: Great points. And as you mentioned before, it's important for the patients who see the provider to discuss their family history-- close and distant family history as much as they can, and they can even ask whether they need to see genetic counselors. Sometimes the patients can remind a busy provider how important that is and ask for a referral, it’s definitely important to ask the provider.  Very quickly, Marianne, you mentioned before the value of testing for both the patient and the broader family in terms of what we call cascade testing and cancer prevention. You mentioned the example in your patient, can you very briefly comment on that and what is the value here again for the patient and the family?

Dr. Dubard-Gault: Absolutely. And sometimes someone with a genetic predisposition, so someone born with a genetic predisposition to cancer, can be at risk of more than 1 cancer in their lifetime. So sometimes, when they're diagnosed with the cancer, we find this genetic predisposition to said cancer, but it may come with other cancers as well, just like the bladder cancer and uterine cancer and colon cancer. And this may not be something a person would want to hear when they're diagnosed with cancer, but it is good information that will stay there for the future as they go through the treatment for having interventions done, right? So it's good information to talk about with their doctors so their doctors can order the colonoscopy or different screening protocol. We'll recognize a certain intervention like removing the uterus of someone in the family so they would reduce their risk of uterine cancer. And obviously, genetic mutations tend to be shared in the family. It's most likely something was inherited in the family rather than new in a person. So each person who's positive for a genetic predisposition, we think about their siblings, their children, their nieces and nephews, and those people may have exactly the same genetic predisposition or mutation, and they may be at risk of the same kinds of cancers. And that's the reason why they would get this information to be eligible for other screenings as well. And interventions.

Dr. Grivas: Very important, and very useful for the patient. Before we wrap up, Marianne, can you comment a little bit on barriers to testing, out-of-pocket costs, culture, trust, literacy, busy practice, competing priorities?

Dr. Dubard-Gault: Yes, absolutely. I think the main ones are awareness that bladder cancer can be a genetic cancer. It's really rare, but it can be. And so keeping that in mind, because then if you're not even referred or that doesn't come to mind, it may not get us to doing this genetic testing. The diagnosis of cancer is a lot to take in, right? So it may not be the right time to do it right away, but keeping that in mind for the future is also important. The cost. Sometimes the generic testing isn't covered by Medicare, unless there are specific criteria that we talked about, a family history of specific type or early diagnosis and all these things. And the genetic counselor will really help push to find as much information as possible to get the test covered. And there are lower-cost options out there. And I think the last 2 are really the privacy of the results. People worry that this information will be shared outside of health care, and/or sharing themselves this information with their family members when they're probably or maybe not ready to disclose their cancer diagnosis. So I find that that's maybe less or lower on the list, but in order to keep in mind as well.

Dr. Grivas: Thank you, Marianne. Maybe the last 2 very quick questions for you. Germline testing and options and value of counseling. I know you have touched upon that already. But did you have any departing thoughts on that part on the value on the patient and the family and any other considerations, for example, DNA biobank, etc.?

Dr. Dubard-Gault: Absolutely. So, I find that meeting with the genetic counselor, even after you've had genetic testing and the results are back, is a valuable thing to do. And not necessarily right away, but later on down the road, right? So because this field, the genetics field, advances rapidly, it's possible someone will be testing again or there are more genes or more mutations out there we weren't testing for a few years ago that we would test again. So keeping in mind, we can test again. And that meeting with the genetic counselor is always useful even if you have heard a little bit about it already. And then the DNA biobanking piece, if that's a service that's available to you, keeping your DNA for the future, when the technology is not advanced yet, is very important because we know for sure the knowledge will change and will bring new treatments and new options for screening and interventions, so keeping the DNA for the future is very useful.

Dr. Grivas: That's a great point. And because technology is evolving very fast, the methodologies are changing, many times we have the information and genetics team, and counselors and geneticists try to keep track and follow those people who are tested to see if any of the information may potentially make a mutation that was of a certain significance-- something that may be significant down the road as more information are coming in. And because of this rapidly evolving nature of information, it is good for people with cancer and also any affected family members to stay in touch periodically and follow up with the genetics team. Maybe the last question for you, Marianne, is if you have any take-home message for our people, our audience today so they can remember going forward.

Dr. Dubard-Gault: Information is power. It really is. And having this information helps your doctors bring the best treatment to the tumor that you have and not somebody else's, right? And for the family, that may bring an answer that was longed for really generations before you, and that would help not only have this information, but take it forward and say, "You know what? I'm going to do something about it because we can." So to me, that's the reason I transitioned careers, and that's the message that I want to keep sharing.

Dr. Grivas: What a great message by Dr. Dubard-Gault. And now we're trying hard to involve and engage genetic counselors and geneticists to our multidisciplinary clinics. And bladder cancer is a great model for multidisciplinary approach, and we try to engage them earlier. So we need more of you, Dr. Dubard-Gault. We need more geneticists and genetic counselors. And with your background in oncology, it's fantastic to work with you. Thanks again for a great discussion. Thanks again to Cancer.Net for all they do for the mission of patient education and of course ASCO. And thanks to the audience for your attention today. Thank you.

Dr. Dubard-Gault: Thank you for inviting me.

ASCO: Thank you, Dr. Grivas and Dr. Dubard-Gault. Learn more about genetic testing and cancer at www.cancer.net/genetics. 

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Christopher Flowers covers new research in non-Hodgkin lymphoma presented at the 2022 American Society of Hematology Annual Meeting, held December 10-13 in New Orleans, Louisiana.

Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and was appointed Division Head ad interim of Cancer Medicine in August 2020.

View Dr. Flowers’ disclosures at Cancer.Net.

Dr. Flowers: Hello and welcome to this Cancer.Net podcast. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center. And it's my great pleasure to talk to you today about updates in lymphoma from this year's American Society of Hematology meeting in December of 2022. I have a number of disclosures related to my work as a consultant for companies in the development of therapies for lymphoma. I will not talk about agents specifically related to those companies, but 2 companies that overlap with some of the areas that I'll talk about in bispecific antibodies includes Genentech, Roche, and Genmab, as well as research support from those companies for research that is performed at MD Anderson. So this year's American Society of Hematology meeting had a number of highlights. I was very fortunate to be the introducer for one of those key highlights, and that was the abstract presented at this year's plenary session. This was actually the first abstract presented in the plenary session where I introduced the abstract and set the context, and Dr. Martin Dreyling from the German group described the TRIANGLE study. So the TRIANGLE study was a randomized controlled clinical trial, meaning that the trial was performed in a randomized fashion to be able to test 3 particular strategies for patients with mantle cell lymphoma.

Mantle cell lymphoma, as many of you may know, is a relatively uncommon form of non-Hodgkin lymphoma. It's a kind of lymphoma that can be quite aggressive, and particularly for younger patients who are suitable for aggressive therapy, the role of autologous stem cell transplantation has been something that's been important for the first-line therapy for mantle cell lymphoma. This study evaluated the use of a standard regimen of giving R-CHOP chemotherapy alternating with R-DHAP chemotherapy. So a chemotherapy regimen that includes Ara-C as their component followed by autologous stem cell transplantation. And it compared using that same regimen to giving it with ibrutinib added to the R-CHOP portion of the chemotherapy, followed by ibrutinib maintenance after the stem cell transplant or another experimental arm that added ibrutinib to the R-CHOP portion of the chemotherapy and gave 2 years of ibrutinib maintenance without stem cell transplantation. I think, importantly, this arm compared to each of those 2 experimental arms versus the standard of care and showed graphically that both of the arms that contained ibrutinib, the BTK inhibitor, looked to have improved failure-free survival compared to the standard stem cell transplant arm. Formal statistical tests were performed to compare the arm that included transplant plus ibrutinib showing that that was superior to transplant alone. And it remains to be seen whether that arm is superior to the arm that used ibrutinib alone.

But those 2 arms look fairly similar in terms of their outcomes, and also the toxicity associated with the transplant obviously was substantially more than performing the therapy without transplant. This suggested perhaps autologous stem cell transplantation can be removed from frontline therapy for patients with aggressive mantle cell lymphoma and provides provocative data that may help to change practice, both in Europe and in the United States, as well as the rest of the world.

A few other abstracts that were presented at this year's ASH meeting presented provocative data about ways to be able to improve the ways that we predict outcomes for patients. Matt Maurer presented the results of the Follicular Lymphoma International Prognostic Index 24, or the FLIPI24, as a risk factor to try and predict patients who might have early progression of disease with follicular lymphoma. One of the things that we know is that when you look at patients with follicular lymphoma, those patients who have progression of their disease within 24 months of the start of chemoimmunotherapy are patients that have markedly worse outcomes. And Dr. Maurer and our colleagues led an international study showing that a new prognostic factor model that included age, hemoglobin, white blood cell count, normalized lactate dehydrogenase, and beta-2-microglobulin, so all laboratory values that are connected within routine clinical practice, along with age, were a better predictor of this early progression of disease. This may serve as a useful model moving forward to help patients and their providers to understand who are the patients who are at higher risk of having aggressive behaving follicular lymphoma, and eventually, we can make strategies that help to address that for those patients.

A second provocative model for using integrated genomics helps to identify patients who also have early progression of disease, and those are for patients with diffuse large B-cell lymphoma. This was presented by Kirsten Wenzel from the Mayo group, where Anne Novak was the senior author for this publication. What they did was they integrated the genomics into the clinical prognostic factors and found that there was a particular RNA-seq profile that helped to identify those patients who had early progression of disease with diffuse large B-cell lymphoma. They compared this approach to other prognostic models and suggested that these approaches may be able to improve upon the prediction of outcomes and be incorporated into the ways that we predict treatment strategies for patients with diffuse large B-cell lymphoma in the future. While these are still early on in their development, I think this holds promise for the future management of patients.

And then the other class of agents that I'll mention from this year's ASH meeting are the bispecific antibodies. There were several abstracts that addressed this, both in patients with relapsing, refractory, diffuse large B-cell lymphoma, and in patient populations with relapsing refractory follicular lymphoma. One of those highlighted came from Nancy Bartlett, who discussed the role of a specific bispecific antibody for patients with relapsed follicular lymphoma. And I think these agents hold broad promise. So I appreciate your time and attention and hope you enjoyed this podcast and look forward to talking to you in the future about new developments in lymphomas broadly.

ASCO: Thank you, Dr. Flowers. You can find more research from recent scientific meetings at www.cancer.net.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

The 2019 ASCO Annual Meeting, held May 31 to June 4, brought together physicians, researchers, patient advocates, and other health care professionals from around the world to present and discuss the latest research in cancer treatment and patient care. In the annual Research Round Up podcast series, Cancer.Net Associate Editors share their thoughts on the most exciting scientific research to come out of this year’s ASCO Annual Meeting and what it means for patients.

First, Dr. Jeffrey Meyerhardt will discuss 4 studies in gastrointestinal cancers, including 1 on colorectal cancer, 1 on gastric cancer, and two studies related to pancreatic cancer.

Dr. Meyerhardt is the Douglas Gray Woodruff Chair in Colorectal Cancer Research, Clinical Director and Senior Physician at the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute, Deputy Clinical Research Officer at the Dana-Farber Cancer Institute, and Professor of Medicine at Harvard Medical School. He is also the Cancer.Net Associate Editor for gastrointestinal cancers.

Dr. Meyerhardt: My name's Jeff Meyerhardt. I'm a gastrointestinal medical oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts. Today I'm going to discuss research on gastrointestinal cancers that were presented at the 2019 ASCO Annual Meeting. And let's talk about four studies: 1 in colon cancer, 1 in gastric cancer, and 2 studies related to pancreatic cancer, all of which are going to affect how patients are treated in the upcoming years.

Starting with the studies on colon cancer, there were 2 additional studies looking at the duration of adjuvant therapy for colon cancer. Adjuvant therapy is the chemotherapy that's given after surgery for people who had a resection of their colon cancer that didn't have evidence of metastases. We give adjuvant therapy to try to prevent and reduce the risk of recurrent disease. The standard of care up till a few years ago was to give 6 months of adjuvant therapy. And for most patients who had stage III or lymph node positive disease, that was 6 months of a fluoropyrimidine, either 5-FU, or an oral form capecitabine with oxaliplatin. This was also given to some patients who have higher-risk stage II disease. Two years ago at ASCO, we learned that giving 3 months of therapy was sufficient, or what we'd describe as non-inferior, for some patients who have stage III colon cancer, particularly those who had what would be considered a better-risk stage II colon cancer, and actually particularly if they got a particular regimen of combining capecitabine and oxaliplatin.

At this year's ASCO, there was a study looking at patients with stage II disease. Most of them had higher-risk stage II disease, something where they didn't have positive lymph nodes, but some other feature that made you a little bit more worried that there was a relatively higher-risk of recurrent disease. And the findings were essentially very similar to what we saw for stage III disease; that for some patients, 3 months of treatment was adequate, particularly if you gave capecitabine/oxaliplatin, and had less toxicity than 6 months of therapy. But if you gave 5-FU/leucovorin/oxaliplatin, a regimen called FOLFOX, 6 months of treatment was necessary. These studies add to the conclusion that first, we can't treat all colon cancers in the adjuvant setting the same, that we should think of them as risk adjustment, and we also have to make decisions regarding what type of treatment, which will help determine the duration of therapy.

The next study I'm going to focus on is looking at gastric cancer and looking specifically at the role of immunotherapy. So what we've already known is that patients who have gastric cancer and esophageal cancer can benefit from immunotherapy in later-line therapy, so after an initial first-line or second-line chemotherapy is no longer helping a patient or is too toxic to continue. The study that was presented at ASCO this year, what is called the KEYNOTE-062 study, was actually looking at 3 different arms of therapy. One was giving a drug pembrolizumab, one of the immunotherapies alone. The second arm was giving chemotherapy alone. And the third arm was giving pembrolizumab with chemotherapy. In looking at what would be the best strategy for patients who are initially being treated for metastatic gastric cancer.

They specifically looked at patients where we think there may be a higher chance of activity. So there are certain ways to look at the tumor and score what's the potential in immunotherapy would be helpful. And this is what's called the CPS score. Patients who had had a CPS score of at least 1, and they also broke it down for people that had even a higher score, greater than 10, in the analysis. And what they found is compared to doing standard chemotherapy, in this case, of fluoropyrimidine, 5-FU, or capecitabine with a platinum, cisplatin, giving pembrolizumab could be non-inferior in terms of overall survival for patients as initial therapy for metastatic gastric cancer; that they saw that in patients who had a CPS score greater than 1. They showed actually that it was superior to give pembrolizumab in terms of overall survival if the CPS score was greater than 10.

What is a little curious in this study is that progression-free survival, which is how long it takes until you have to switch to therapy, wasn't actually better with pembrolizumab compared to chemotherapy for the people who had relatively lower CPS scores. But it was non-inferior for those who had a greater than 10.

The second part of the study was looking at should we give chemotherapy and pembrolizumab at the same time, like the whole kitchen sink, at the same time of both giving chemotherapy and an immunotherapy. And that actually didn't add any benefit to chemotherapy alone. So it was not improvement in overall or progression-free survival.

So what do we conclude from KEYNOTE-062? Well first is that there are some patients where giving an immunotherapy upfront by itself can be just as good as starting chemotherapy, particularly those who have a score that's a relatively higher likelihood of benefiting from immunotherapy. But we also learned that combining them together does not add extra bang for the buck as initial treatment. There should still be a therapy considered later, whether you start with pembrolizumab and then later get chemotherapy or vice versa. But doing them all at the beginning does not seem to add additional benefits.

There were then 2 studies of note for pancreatic cancer. One of them was an adjuvant study, which again, adjuvant therapy is giving chemotherapy after surgery to try to reduce the risk of recurrent disease. What we know for pancreas cancer, there are several options to consider in terms of adjuvant therapy after surgery. For quite a few years now, the standard was giving a drug called gemcitabine. There was then a study looking at gemcitabine with an oral drug called capecitabine, again, the oral form of 5-FU, and that looked to be a little better than gemcitabine alone. And then several years, a study from the Canadian Cancer Treatment Group and then a Unicancer GI PRODIGE Group looked at a combination of folfirinox, a 4-drug regimen that's now very standard for some patients with metastatic pancreas cancer. In looking at that regimen as adjuvant therapy, compared to gemcitabine alone, that study showed a real significant improvement in terms of recurrence rate and disease-free survival for patients who got this 4-drug regimen compared to gemcitabine alone, and has really become a standard for patients who have a good performance status after their surgery.

The current study that was presented at the 2019 ASCO Meeting was looking at a different combination, looking at gemcitabine plus another drug called nab-paclitaxel. It's a combination also used in metastatic pancreatic cancer. It was shown to be better than gemcitabine by itself in metastatic pancreatic cancer. And the hope would be another option for patients in the adjuvant setting. Unfortunately, the study fell a little short in terms of the primary endpoint as initially determined when the protocol was being developed, what was called an independent assessment of disease-free survival. So sending the scans and sending all the data to independent reviewers, and that again just fell a little short statistically. If you look at investigator-assessed disease-free survival, it actually was statistically significant, as well as overall survival. The conclusion for the study is even though it didn't quite meet the mark in terms of what was predefined, it does give suggestion that it is better than giving gemcitabine alone. And there are patients in the adjuvant setting for pancreas cancer where folfirinox is probably not as good of an option: it's a fairly toxic regimen. People who have a performance status having a little more difficulty recovering from the surgery or have more comorbidities, gemcitabine plus nab-paclitaxel probably still should be considered an option for these patients, compared to gemcitabine alone.

The final study, which led to a plenary session, which is basically one of the 4 most attractive abstracts in the 2019 ASCO Annual Meeting this year, was looking at maintenance therapy for people with metastatic pancreatic cancer using what's called a PARP inhibitor olaparib. It was specifically for patients who had received a platinum-based chemotherapy and they had a germline mutation of BRCA. So BRCA mutations are commonly known to affect the risk of developing breast and ovarian cancer. There are 2: BRCA 1 and BRCA 2. Those also have association with increased risk of pancreatic cancer. And what we know is the PARP inhibitor, through what are called DNA repair mechanism, do seem to have activity in these various type of cancers, including for patients with metastatic pancreatic cancer.

This was specifically looking at people who had metastatic pancreatic cancer. Could you get them off the more cytotoxic chemotherapy for a period of time to do something more of what would be considered a maintenance therapy. So having them for period time off toxic therapy and not impacting their overall outcome. It ends up about 4 to 7 percent of metastatic pancreatic cancer patients harbor a BRCA mutation. What we know about BRCA-mutated pancreatic cancers, they have an increased benefit from a platinum-based chemotherapy, cisplatin or oxaliplatin, so patients had to have had a platinum-based therapy to go on the study. They were on chemotherapy for at least 16 weeks and then they were randomized to stop their chemotherapy and receive elaborate versus placebo until there was disease-free, disease progression, or increased toxicity.

And what we saw is that the progression-free survival, the time till they had to restart chemotherapy, actually was doubled with the group receiving the maintenance therapy with olaparib. So that was really an exciting finding and a really important finding where you can get people off of chemotherapy for a period of time until you have to restart chemotherapy. Now there is not a survival benefit that was noted yet on the study. It is still very early to look at overall survival. There are also patients who are able to crossover in terms they got olaparib, another part in their cancer treatment, because of the known benefit in metastatic disease. So overall survival may be a little harder to fully interpret, but I do think that this will become a standard for patients with BRCA-mutated colorectal cancers, to receive chemotherapy for some period of time, several months, and then if they're doing well, then to switch them to a maintenance therapy.

So that is our summary of the GI cancer research from the 2019 ASCO Annual Meeting. Again, my name is Jeffrey Meyerhardt, and thank you for listening.

ASCO: Thank you, Dr. Meyerhardt.

Next, Dr. Guillermo Garcia-Manero will discuss a study on a new immunotherapy drug that offers promising results in patients with acute myeloid leukemia or myelodysplastic syndromes, as well as 2 additional studies that looked at t-cell therapies.

Dr. Garcia-Manero is the Deputy Chair of Translational Research and Professor, Department of Leukemia, at The University of Texas MD Anderson Cancer Center in Houston, Texas, and the Chief of the Section of Myelodysplastic Syndromes at MD Anderson Cancer Center. He is also the Cancer.Net Associate Editor for Leukemia.

Dr. Garcia-Manero: Hello. I am Guillermo Garcia-Manero. I am a professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center. I'm very happy to summarize some of the key presentations at this year's ASCO meeting in Chicago. Of course, ASCO is big on solid tumor malignancies, but there is more and more information regarding leukemia treatment for our patients, also, at the meeting. This year, there were a number of very interesting presentations. First, I want to start briefly saying that there was a very interesting educational symposium where Drs. Al-Kali, Sekeres, Craddock, and myself discussed how to use these hypomethylating agents, drugs like azacitidine or decitabine in patients with leukemia. This meeting was very well attended by multiple community physicians that attend ASCO, and it contained, I think, very useful information in terms of the use of these compounds for our patients.

In terms of research presentations, there were multiple. The one that I actually felt was perhaps more interesting was a presentation by Dr. Sallman from the Moffitt Cancer Center in Tampa where he was describing the first results of a new therapy for patients with MDS and AML and potentially other hematological malignancies and cancers known as Hu5F9-G4. This agent is an antibody that targets a molecule called CD47. This was discovered by Dr. Maute and Dr. Weissman at Stanford. It is known to be a “don’t eat me” signal in a way kind of an alternative immune checkpoint inhibitor type of process. But this is interesting because it's focusing more around macrophages more than lymphocytes and it could have a broad use, again, not only in leukemia and hematological malignancies but potentially many other cancers.

I think that this data is very striking because the results of Dr. Sallman indicate a very high level of activity with the combination of the hypomethylating agent azacitidine, in this case, both in MDS and AML. This was agnostic of molecular and cytogenetic alterations. It was well tolerated, although there was a little bit of anemia early on with administration of this therapy. But I think this was one of the most innovative and promising new potential therapies for our patients with leukemia. This drug has been shown to be active in lymphoma and now, we expect that the studies initially done in the UK and in Tampa are going to be expanded to other centers in North America, and they may actually provide with a very interesting innovative and very active new form of therapy for our patients. So I thought that was the most innovative presentation at the ASCO meeting.

Of course, there were multiple other presentations. There was additional data on new FLT3 inhibitor known as gilteritinib. This drug recently approved for patients with AML. There was also further information on a new compound known as CX-01 for patients with acute myelogenous leukemia. Again, this is an interesting compound that seems to be a heparin analog, and the early studies are showing significant activity as well for our patients. There was also very interesting data in terms of the phase I results of the ZUMA-3 trial. This is a CAR T-cell type of approach for refractory patients with acute lymphocytic leukemia. And finally, this interesting presentation from the MD Anderson group with an off-the-shelf viral-specific T-cell therapy against patients with adenovirus disease that are immunosuppressed. It's actually very important in a way-- kind of similar therapies for patients that have viral complications, this group have shown, actually, significant activity of similar type of approaches for patients with BK virus and other conditions.

So in summary, I think that the meeting was very important like it is every year. I think that we're starting to see presentations at ASCO for new agents of high relevance. I think that the community, at least in MDS and AML, it is very interested on the follow-up with the Hu5F9-G4 agent in combination with AZA for MDS and AML. And we're looking forward to be part and see the results of expanded phase II and potential phase III studies with this compound. And with that, I want to thank you for your attention.

ASCO: Thank you Dr. Garcia-Manero.

Learn more about these topics and other research presented at the 2019 ASCO Annual Meeting at www.cancer.net, including additional Research Round Up podcasts. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network, a collection of 9 programs covering a range of educational and scientific content offering insight into the world of cancer care. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

[music]

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In today’s podcast, Dr. Timothy Gilligan and Liz Salmi will discuss their article “Patient-Clinician Communication Is a Joint Creation: Working Together Toward Well-Being,” from the 2018 ASCO Educational Book. They cover several ways people with cancer and members of their health care team can work together in order to improve their communication, including a study on sharing clinical notes with patients, a recent guideline from ASCO on physician-patient communication, ways to address religion and spirituality, and tips for patients.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Center. Ms. Salmi is a brain tumor survivor, and Senior Strategist in Outreach and Communications for OpenNotes.

Published annually, the Educational Book is a collection of articles written by ASCO Annual Meeting speakers and oncology experts. Each volume highlights the most compelling research and developments across the multidisciplinary fields of oncology.

ASCO would like to thank Dr. Gilligan and Ms. Salmi for discussing this topic.

Dr. Gilligan: Hello, my name is Dr. Timothy Gilligan from the Cleveland Clinic. I'm joined today by Liz Salmi of OpenNotes and the Beth Israel Deaconess Medical Center. In this podcast, we will be sharing some key points from our 2018 ASCO Educational Book article titled “Patient-Clinician Communication Is a Joint Creation: Working Together Toward Well-Being.” I would also note that Dr. Andrea Enzinger from Dana-Farber was an author on that.

So, Liz, we were going to start with talking about your piece on this, your work with OpenNotes. And for those who haven't heard of this, the idea is making progress notes openly available to patients so they can read the progress notes about their medical care. Can you talk a little bit more about what OpenNotes is and what's at stake here?

Liz Salmi: Sure. Absolutely. Thanks for that intro. And I just want to say my role at OpenNotes—I do outreach and communication work, but, also, I think it's important for the audience to know that I am also a patient. I'm a person living with a malignant brain tumor or brain cancer. And I'm now a 10-year survivor, but I'm still living with active disease. So what I'm talking about today is not just part of my job, but it's also very personal to me. And so what you just kind of gave me a lead-in on, is explaining what OpenNotes is, but I do want to repeat a little bit about that. So OpenNotes is now a national movement that stems from real medical research, and it's a movement dedicated to making healthcare more open and transparent by giving people—or patients—access to their doctors' notes via existing secure online patient portals.

And when I say that, I want to make it clear that OpenNotes is not a product, or it's not a piece of software. It's more of just a concept of let's give patients full access to their medical records. And when we talk about OpenNotes, a lot of patients will say, "Well, what is a doctor's note?" Right now, I, as a person, can login to my digital online portal to email with my doctor, or, say, set up appointments, or order prescription refills. And sometimes, after a visit I can see a visit summary of a little bit of what transpired at my visit with my doctor. But what I don't see is my clinical notes.

Now, clinical notes, a lot of people and patients don't realize that after every clinical visit with a doctor, they go back to their office and write up these really detailed notes of everything that transpired during the visit. But most patients, about 93% of the US population, don't have access to this information. And it's a bummer because that information is so detailed. And as a person living with cancer, I'm kind of dealing with something that's emotional and overwhelming, and most people can't remember everything that their doctor says. And most doctors keep track of all of this in their clinical notes.

And OpenNotes, as a research project, was looking into what would happen if we gave people or patients easy access to those clinical notes that the doctors write. Would they understand those notes? Would they get some sort of benefit or value out of it? What would doctors think about that? And so I want to talk about what that original study is, and I'll hopefully try to do it quickly. But OpenNotes started as this research project. It was conducted in 2010, the first project, and it has now been replicated at multiple sites around the country. The original research was done with over 100 primary care doctors and 20,000 patients. And we tested this concept of sharing notes at 3 sites, at the Beth Israel Deaconess Medical Center in Boston, at Geisinger Health in Pennsylvania, and at Harborview Medical Center in Seattle.

And at the beginning of the project, they asked all the clinicians who'd be sharing their notes, "What do you think's going to happen?" And the doctors thought, "Gosh, we write these notes at such a high level because it's a communications tool with our other colleagues. And we don't think our patients are going to really understand what we're writing. And we're also concerned that patients might be afraid of what they read because there's all kinds of stuff we capture in there." And they also surveyed those patients. Before they received their notes, they surveyed them and said, "What do you think's going to happen? You're going to now read your notes for the next year. What do you think?" And patients, even people like me, were like, "I don't know what to expect. I've never seen this type of information before."

So fast-forward to a year later, and what they found was that during that year about 80% of patients read a note, and 75% of patients reported benefits. They felt like, "Wow, if I can read my doctor's notes, I feel more engaged in my care. I better understand why certain medications were prescribed to me. I felt like I had more control over my care." Sharing the notes improved the doctor-patient relationship. 99% of patients felt better or the same after reading just one of their doctor's notes. They felt they could trust their doctors more. And, just like regular people, sometimes doctors make mistakes. And sometimes those mistakes would transfer to their clinical notes, and patients, when they're reading those notes, were able to point out errors. For example, the doctor might write, "There's a problem with your left knee." And the patient will say, "Actually, I was talking about my right knee." So there was this opportunity for a little bit of quality control.

Dr. Gilligan: Well, thank you. So you've outlined, obviously, some of the benefits to patients in terms of direct access to information, the opportunity to correct mistakes, the chance to feel more empowered. I'm curious. Often, we hear from clinicians fears that this is going to generate a lot more phone calls or problems, or patients will get upset. Can you talk just a little bit more about what the research has shown in terms of what has actually happened when this has been turned on, so to speak?

Liz Salmi: Absolutely. So we've learned a lot. They're concerned that by sharing their notes, it's going to increase that doctor or other clinician's workflow, meaning if a patient reads a note and anything about it is unclear, or maybe there's a word and phrase they don't know, it's going to trigger an email or a phone call back to the doctor. So mainly, the concern is workflow. And we've seen—and it continues to show—that workflow does not increase. W

hy is that? Well, often, a patient will go to a visit, leave that doctor's visit, and then later go, "Oh, my gosh. I can't remember what my doctor said." If they don't have access to their notes, that triggers an email or maybe a phone call saying, "Oh, hey, Doc. I can't remember. Did you tell me to do this or that?" or, "How many times am I supposed to take this medication?" or, "How many exercises do I need to do each week?" or, "What was that thing you said?" With OpenNotes, patients can actually go back to the doctor's notes, the exact record of that interaction, and refer to the note itself. So that decreases the need for another email or another phone call.

Occasionally, a patient might read a note and have a question that the note triggers. So then they might follow up with a question through email or a phone call. So the 2 kind of cancel each other out, and, overall, you don't see an increase in workflow.

Also, they’re worries that most doctors have in advance of sharing notes. "Oh, my gosh.  I think my patient is going to read what I write, and they're going to get stressed out by it." But that never happens. And what is written in a medical record and in a note is what the doctor actually says to the patient. So there shouldn't be any new information, necessarily, in the note. An interesting thing to think about is that after that original study, all the doctors who shared their notes after that entire year were allowed to stop sharing their notes, but not a single 1 did. They were like, "Oh. This is working out for me. My patients seem to like it. So I'll keep going."

Dr. Gilligan: So I want to use that as a segue because we have two other subjects we need to cover in this podcast. Both in the article and in the session we did, we talked about the new ASCO patient-clinician communication guidelines, the first guideline that's been published. And that was published late 2017.

The guideline was broken down into 9 key areas that we thought were important. One was just core communication skills. How do you have the conversation in a better way?

One thing that's often unappreciated is that a lot of Americans have low health literacy. They have low numeracy. If we say to a patient, "There's a 30% chance of this or that," that may sound very obvious to us what it means, but it often is misinterpreted. And even lay persons, what we might consider average or normal numeracy or literacy, don't take in the numbers they get from healthcare professionals as fluently as they think they do, and there are better and worse ways that have been studied of doing that, and we talk about that.

Cost of care is a new issue. Bankruptcy from healthcare is a large problem in this country. There's a lot of unaffordable drugs out there, so how to talk about that is an issue that comes up in it.

Underserved population is a concern that we address, whether it's racial or ethnic minorities or other underserved populations. The LGBT community and their healthcare needs is increasingly recognized, and ways in which they encounter challenges in the healthcare setting a problem, so we talk about that.

And then lastly, the issue of how do we train people to get better? There's been a lot of research in how people improve in communication, and I think the big take home from that is that communication is a motor skill. It's like learning how to play a sport or a musical instrument, and the way people get better at it is by practicing it and then getting feedback so that they can improve.

And then the last piece that I really wanted to get your thoughts about was how do we talk about spirituality for patients with patients? We know that from studies of patients and surveys that the majority of patients think spirituality, whether or not that's formal religion, but spirituality in general, is important to them in coping with serious illness, and yet it's something that many providers feel unprepared or unskilled at in terms of bringing up. So in a sense, this links in with the former topic of key communication skills. I'm curious your thoughts, as a patient, what you think about the issue of spirituality and how it can be helpful to patients going through a difficult time.

Liz Salmi: Yeah, no, absolutely. And thanks for clarifying. There's formal religion and then there's just kind of general spirituality, kind of a vague aspect or a way of looking at things. And, I think, as a person who-- I don't attend church, but I do think about how I view my place in the world and as that relates to my cancer experience is they kind of go hand-in-hand.

And when I was first diagnosed, realized I had a brain tumor, and then I had a brain surgery, and I'm laying in the hospital 24 hours later, and a chaplain walked into the room and introduced himself and said, "Hey, I'm the hospital chaplain. And I just want to let you know that I'm here to talk to you." They are basically offering their support. But as a new patient and someone who's never been in the hospital before, I had no idea what the role of the chaplain was. And I told the person. I was like, "Yeah, I don't want to talk to you right now. What are you doing here?"

And they also scared me. The presence of a chaplain, I had only seen from TV that if a religious person came into a hospital room it meant somebody was dying. And I was like, "I just had brain surgery 24 hours ago. They're sending in a religious person to see me. Does that mean I'm dying?" So it freaked me out, and I told the person, "No, I don't want to see you. Please leave." And then when the nurse came in to check on me, I said, "What was that all about?" and the nurse says, "Oh, if you don't want a chaplain to come see you, I can make a note to not have them come see you again." I said, "Yeah, please do that."

So, actually, in my medical record, someone made a note in my inpatient notes, "Patient refuses chaplaincy services." And it wasn't until 2 years ago, so like 8 years after diagnosis and that first brain surgery that I learned a chaplain is non-denominational. They're there just talking about psychosocial, spiritual issues, that it has nothing to do with a particular religion at all. They're just there to help. And I think it's a bummer and a disservice that I didn't find out until eight years later when, really, I probably could have benefited from having someone to talk to from that perspective.

Dr. Gilligan: I think the promise here is that if we feel confident that we have the tools to do this, and we know how to have the conversations, and then we start having them, we'll be taking better care of our patients because they're telling us in surveys over and over again that this is important to them, and it would help them if they could talk about it. But it has to be done in a skilled way. And as your story, Liz, tells, if it's not done that way, then it can be unhelpful. It reminds me of Rana Awdish in her book In Shock talks about story where she wakes up in the ICU, and she's getting last rites. And that's not really the way you want to be introduced to a priest [laughter].

Liz Salmi: No way. That's wild.

Dr. Gilligan: It was kind of shocking to her at the time. Obviously, she survived to write about it, thank God.

Liz Salmi:  Well, you talk about these communication guidelines, which are for doctors to help them better understand how to communicate well with patients, but I was just curious if you have a couple tips for the listeners who, mainly, are patients for this podcast. What can patients do to help ensure smooth communication with our healthcare team? Do you have any tips for us if we want to kind of take control of situation a little bit?

Dr. Gilligan: Yeah, no, that's a great question. So 1 of the things I find interesting about that is that in the early research on the impact of communication on patient medical outcomes, it was documented very early that outcomes in managing high blood pressure, managing diabetes, other hard medical outcomes, not the more patient-satisfaction, softer stuff-- that hard outcomes improved if you either taught clinicians to communicate better or taught patients to communicate better. Either one has a positive impact on healthcare, so it's very appropriate to ask. The reason we focus on training clinicians is there are many fewer clinicians than there are patients out there. Training all the patients in the world would be a lot of people to train.

I think the most important thing is to come organized, to have it very clear what your priorities are, and what you're hoping to accomplish, and to try to lay that out early in the appointment. And it's helpful for us clinicians to know, but it's also helpful to advocate for yourself if you come in with a clear sense of what your goals are and what you're hoping to get out of the encounter.

I think the other thing I would say is it's really helpful to bring someone with you. I think if I'm ever in the hospital, I would want a family member there. And if I ever have a family member in the hospital, I'm going to be there, too, because in the modern healthcare system you need to advocate for yourself. And so I think being prepared and organized is one way you can advocate for yourself. Bringing someone with you can help, as well.

The last thing I would say is the model of communication skills that we teach is really built around building stronger relationships between clinicians and patients. And I think that, on both sides, it's a 2-way street, that relationship. If we both pay attention to the fact that we will work together much more effectively if we have a strong relationship, then we can try to communicate with each other in a way that helps build that up.

Illness is stressful. People get upset. They get angry, and all that is natural. But the more we can remember that, in the end, we're on the same team, we're kind of rolling the same direction. I usually find myself saying this to clinicians to try to avoid getting into unnecessary conflict with patients. But I think also, too, on the patient side. So those would be the 3 things I would really think about: being organized, bringing a family member with you when possible—I realize it's not always possible—and then paying attention to the nature of the relationship and attending to the relationship, not just the work that you're trying to get done. There's certainly more I could say, but it's a big subject.

Liz Salmi: Yeah, no, absolutely. And thank you for that. It was really helpful. I know, from an OpenNotes perspective, we often realize that access to information also helps ensure smooth communication. And when doctors and patients are on the same page and able to look at some of the same information, a patient's level of understanding increases. And it helps us make better decisions overall.

Dr. Gilligan: I agree, 1 of the things I like about giving patients more access to information is 1 of the things I, in a sense, challenge patients to do is to take more ownership over their own care. They should know what medications they're on, and they should know why they're on them, and they should know why they take them. I don't say that in a critical sense, but just if it's me, and someone has me on medication, I want to know why, and I want to know which drugs I'm taking. And keeping track of that, I think, taking more ownership over that, and really knowing your medical history to the best extent that you can helps you get better care in our system.

Liz Salmi: Yeah. Absolutely. High five on that one.

Dr. Gilligan: Well, it's been great talking to you again, and--

Liz Salmi: Same. Yeah, and thank you. It was a pleasure to get to write this article with you in the ASCO Educational Book, which, I believe, anyone can read at ASCO.org/edbook.

Dr. Gilligan: That's right. That's right. So look it up, take a look. We hope that you enjoy it. Thank you for listening to our podcast.

ASCO: Thank you Dr. Gilligan and Ms. Salmi. Please visit ASCO.org/edbook to read the full article. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

Cancer.Net is supported by ASCO’s Conquer Cancer Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

[music]

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Cancer.Net Associate Editor Dr. Norah Lynn Henry discusses several studies presented at the 2019 San Antonio Breast Cancer Symposium, held December tenth through fourteenth in San Antonio, Texas. Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. View Dr. Henry’s disclosures at Cancer.Net.

ASCO would like to thank Dr. Henry for discussing this research.

Dr. Henry: Hello. I'm Dr. Lynn Henry from the Rogel Cancer Center at the University of Michigan. I would like to share with you a few of the research highlights related to breast cancer from the recent 2019 San Antonio Breast Cancer Symposium. I do not have any relationships to disclose related to these studies.

Many of the exciting trials that were presented at this conference were for treatment of HER2-positive breast cancer. This is a specific type of breast cancer that accounts for about 1 in 5 breast cancers. Both of the studies I'm going to discuss related to HER2 involve treatment of patients with metastatic HER2-positive breast cancer or cancer that has spread beyond the breast and surrounding lymph nodes.

The first trial is called HER2CLIMB. This is a phase III trial examining a new drug called tucatinib that is a pill that is designed to turn off HER2. Because of the type of drug that it is, it is thought to treat cancer both outside and inside of the brain which is important because many patients with this specific type of breast cancer can have the cancer spread to the brain. Patients who enrolled on this trial had previously been treated with multiple different treatments for HER2-positive metastatic breast cancer. In addition, almost half of the patients had metastases or cancer in their brain. In the HER2CLIMB trial, all enrolled patients were treated with the anti-HER2 antibody drug trastuzumab, also called Herceptin, as well as a chemotherapy drug called capecitebine or Xeloda. In addition, two-thirds received the new drug tucatinib and one-third received placebo. Overall, the drug combination was pretty well tolerated by patients with some diarrhea and fatigue. What is exciting about this trial is the patients who were treated with tucatinib had a longer time until their cancer progressed compared to those who took placebo. Those patients who had cancer in their brain got a similar benefit from the drug as those who didn't. In addition, on average, patients were also more likely to live longer if they took the tucatinib drug, an average of 4.5 months longer. This represents a potentially exciting new treatment option for patients with HER2-positive breast cancer. However, it has not yet been approved by the FDA.

The second trial called DESTINY-Breast01 tested another new drug also for HER2-positive breast cancer. This drug is called trastuzumab deruxtecan which is a standard HER2 treatment trastuzumab with a chemotherapy drug attached to it. This was actually a phase II trial in which all patients got the same dose of this new drug in the data that they showed at the meeting. Everyone had been previously treated with a number of different drugs for HER2-positive metastatic breast cancer. In general, patients tolerated the treatment relatively well although some experienced lowered blood counts, hair loss, and inflammation of their lung. In this trial, almost two-thirds of the patient had at least partial shrinkage of their tumor and the average length of time that patients were able to continue taking the medicine was more than a year. This drug also represents a potentially exciting new treatment option for patients with HER2-positive metastatic breast cancer although it also has not yet been approved by the FDA. We are hoping that both of these drugs will get approved in the near future.

Switching gears a bit, I will now mention a study that looked at a treatment for triple-negative breast cancer or cancer that is negative for estrogen receptor, progesterone receptor, and HER2 receptor. About 10% of all breast cancers are this type of cancer. A number of different trials have looked at using an oral chemotherapy drug called capecitabine beans or Xeloda for treatment of stage 1 to 3 triple-negative breast cancer. Studies have either looked at adding capecitabine to standard chemotherapy at the same time or using it as an additional treatment following completion of standard chemotherapy. However, to date, very few studies have shown that adding it is actually helpful. The investigators who presented their findings at the San Antonio meeting combined all the data from the trials that had been conducted so far, something called a meta-analysis. What they found was that specifically for the patients with triple-negative breast cancer, adding capecitabine to the treatment after the standard chemotherapy has been completed, decreased the likelihood of cancer returning and increase the overall survival of the patients. This was not the case for patients with other types of breast cancer including hormone receptor-positive and HER2-positive.

In order to maximize the benefit for patients and minimize the toxic effects of treatment, not all patients with triple-negative breast cancer should take capecitabine. Rather, those who have a higher chance of their cancer returning such as patients who get upfront chemotherapy and still have cancer left at the time of surgery should talk with their oncologists about whether capecitabine is a good choice for them.

One question that we cannot currently address is which patients are at higher risk for their cancer returning. In order to partially answer this question, a study was presented that examined compounds in the blood to see if they could be used to determine the likelihood of cancer returning in the future. Investigators looked at specific cancer compounds in the blood of patients who had been treated for stage 1 to 3 triple-negative breast cancer. Patients had blood samples drawn soon after surgery to look at both DNA from the cancer circulating in the blood, as well as cancer cells circulating in the blood. Those who had both DNA and cancer cells detectable in their blood were more likely to have their cancer return compared to those who didn't have either DNA or cancer cells in the blood. Those who had one but not the other were somewhere in between.

Although we currently don't know how best to use this information when caring for our patients, and therefore this is unlikely to be something that your oncologists will order for you at this time, tests like this are likely to become commonplace in the future once we have more data. One final study I would like to mention is related to estrogen receptor-positive breast cancer. The NSABP B-42 clinical trial is addressing the question of how long postmenopausal women with hormone receptor-positive breast cancer should be treated with aromatase inhibitor therapy. The investigators compared 5 years versus 10 years. The trial was completed a while ago. And now that they have followed patients on trial for a full 10 years, the investigators have shown that taking the aromatase inhibitor letrozole for 10 years instead of 5, reduced the chance of having breast cancer return in the future. However, the benefit was relatively small.

Therefore, since the benefit was relatively small and there is a risk of side effects from continuing to take the medicine, it is important for patients and oncologists to consider each patient's individual situation and risk of cancer returning when making the decision about how long she should take the medicine. In addition, there is more research going on that should provide additional information about how much benefit an individual patient is likely to get from this prolonged therapy. Overall, there is a lot of exciting research going on across all the different subsets of breast cancer.

As you can see, the results of many important clinical trials were reported at the recent San Antonio Breast Cancer meeting and there are many more clinical trials ongoing that will hopefully result in the approval of multiple new effective treatments for breast cancer. In addition, there is research going on that is examining the impact of treatment on patients with breast cancer and trying to improve the lives of those living with breast cancer. Finally, there are even more trials going on trying to figure out how best to prevent breast cancer from occurring in the first place. Clinical trials are critical for the development of these new treatments.

Well, that's it for this quick summary of this important research from the 2019 San Antonio Breast Cancer Symposium. Overall, we continue on a fast track in breast cancer with many new and exciting therapies being actively studied and research helping support our patients do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you very much.

ASCO: Thank you, Dr. Henry.  Learn more about breast cancer at www.cancer.net/breast. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available. 

Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today’s podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across prostate, bladder, and kidney cancer.

This podcast will be led by Dr. Brian Shuch, Dr. Neeraj Agarwal, Dr. Petros Grivas, and Dr. Sumanta (Monty) Pal.

Dr. Shuch is the director of the Kidney Cancer Program at UCLA Health and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at the institution. He has served in a consulting or advisory role for Bristol-Myers Squibb.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb, Exelixis, and Merck.

Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. He has served in a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb, Exelixis, and Merck.

Dr. Pal is co-director of City of Hope's Kidney Cancer Program and is the head of the kidney and bladder cancer disease team at the institution. He has served in a consulting or advisory role for Bristol-Myers Squibb and Exelixis.

View full disclosures for Dr. Shuch, Dr. Agarwal, Dr. Grivas, and Dr. Pal at Cancer.Net.

Dr. Shuch: Hi, I'm Dr. Brian Shuch from UCLA's Institute of Urologic Oncology. And I'm really thrilled to moderate today's Cancer.Net podcast on GU clinical trials. I'm joined today by Dr. Neeraj Agarwal from Utah's Huntsman Cancer Center, Dr. Petros Grivas from the University of Washington's Fred Hutch Cancer Center, and Dr. Sumanta Pal from the City of Hope Cancer Center. Thanks for being here today, and we'll jump in to discuss 3 clinical trials in the urologic cancer space, one for prostate, one for bladder, and one for kidney cancer. Let's discuss some of the goals of clinical research first, okay? Neeraj, can you let us know what is the purpose of a clinical trial, and the ultimate goal?

Dr. Agarwal: All these clinical trials aim to identify better treatments with the hope that the treatment will be safe and effective. An ultimate goal for all the clinical trials is to get approval [from the FDA for the routine use of the new treatments being tested.] I'd like to add, that the way I explain this to my patient, a clinical trial is the only way I can get cutting-edge therapy for my patients in my clinic without having to wait for many years for FDA approval of those drugs.

Dr. Shuch: Petros, it seems that patient engagement is really essential to this type of clinical research. What is the patient's role here, and what can they expect by participation in a clinical study?

Dr. Grivas: They can directly help [the research team] define better treatments and also improve existing therapies. And they can do that by either participating in clinical trials directly, and can also help us find the clinical questions. And the patient advocate groups are helping us do that by giving us input how to design clinical trials. And, of course, a number of trials that we're conducting are focusing on disease prevention or treatment of the cancer. And I think the patient's role overall is critical in every patient who's asked their provider about clinical trials.

Dr. Shuch: So Monty, for your patients, how do you ensure patients are safe when they participate on these types of trials?

Dr. Pal: Safety is our primary concern when conducting a research study. The patients are taking risks by participating, and these risks should be very clearly delineated in the context of a consent form. It's really critical that we, as investigators, perform very close monitoring in association with our patients. But we also have very intensive oversight of our clinical trials by independent monitoring committees, by the drug companies, and even the FDA. Now, trials can actually be closed early if there are safety concerns that emerge, or if drugs don't appear to be effective. Keep that in mind.

Dr. Shuch: Got it. It's reassuring that for these types of trials, there's very close monitoring. So Petros, with the potential risk that we discussed, why would a patient participate? What are the benefits here?

Dr. Grivas: Brian, this is a critical question. And I think the purpose of cancer research and clinical trials is to try to benefit the patient individually, but also to try to move the field forward, in terms of more knowledge about cancer research, also benefit the community and the society, in general.

Dr. Shuch: How does a patient identify if a clinical trial's right for them? And how can they potentially participate?

Dr. Agarwal: I think the most important role is of the physician who is seeing the patient. And the physician may alert you to a specific clinical trial that is focused on your current condition. So maybe 10 or 15 or 20 clinical trials you saw on the Huntsman Cancer Institute website, but maybe 1 or 2 are specifically needed for a patient's given situation. Also, not every center has a clinical trial for every condition.

Dr. Shuch: We’ll jump in to discuss 3 clinical trials that were chosen by members of Cancer.Net editorial board for genitourinary cancers. And they were basically chosen from the Trials in Progress abstracts that were submitted and presented at the ASCO GU 2020 Symposium. So because these are ongoing clinical trials, we may not have final results for these trials at this time. But I'd like to note that none of the members of this discussion have any direct involvement for these trials. For reference, all relevant disclosures can be found on the notes for this episode of Cancer.Net. So let's jump in. Neeraj, let's discuss the KEYLYNK-010 study. [Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-7339-010/KEYLYNK-010) (KEYLYNK-010)] Can you briefly summarize this study for us?

Dr. Agarwal: So this study is for patients who have progressive metastatic castrate-resistant prostate cancer, meaning the metastatic prostate cancer or advanced prostate cancer, which has already progressed on multiple previous lines of therapy, including chemotherapy and 1 of the novel hormonal therapies, which include enzalutamide and abiraterone. These are all standard therapies which are approved currently by FDA for treatment of our patients. Before I talk about this clinical trial, which includes multiple drugs, which is basically testing a combination of immunotherapy, pembrolizumab, with olaparib, which is a PARP inhibitor—and I'm going to explain those drugs in a moment—and comparing these drugs with other drugs, which are already approved by FDA and include enzalutamide and abiraterone. These drugs are manufactured by Merck, AstraZeneca, Pfizer, and Janssen. And I have consulted on a scientific advisory boards to all these companies and received honoraria for consulting to these companies. 

So with that in the backdrop, I'd like to go ahead and briefly summarize this study. The patients who are progressing on the standard treatment option for metastatic castrate-resistant prostate cancer, including prior chemotherapy, and 1 of these novel hormonal therapies, which include abiraterone or enzalutamide, but not both, these patients are randomized on a 1-on-1 fashion to the novel combination of pembrolizumab with olaparib versus other hormonal therapy, which the patient has not received in the past. The patient's disease has progressed on abiraterone or enzalutamide. Then they are randomized to the novel combination pembrolizumab with olaparib versus abiraterone or enzalutamide.

Dr. Shuch: So Neeraj, what's the current standard of treatment for these patients at this time?

Dr. Agarwal: The current options are very limited. I would say the only chemotherapy, which may be used again, is docetaxel. Sometimes, we re-treat patients with 1 of these drugs on which they have already progressed. Cabazitaxel is another drug which can be used. But please note that by the time patients have already had disease progression on these previous therapies, the expected benefit by trying these currently available options are very limited. Most of the time, patients experience disease progression within 3 to 4 months on these currently-approved medications.

Dr. Shuch: So what is the exact problem that you're trying to solve or show with this study?

Dr. Agarwal: So pembrolizumab is an immunotherapy, and it’s already approved for patients with multiple types of cancer. Olaparib is an oral pill which is already approved for patients with advanced breast cancer and ovarian cancer. Olaparib works by incapacitating the cancer cells from repairing their DNA, which in turns lead to cancer cell death.

Taking a step back, if when we treat patients with olaparib, these cells also get unusually sensitive to action by concomitant treatment with immunotherapy. And this is based on the laboratory data, pretty strong laboratory data. And hence, there is a rationale for combining pembrolizumab with olaparib. And what olaparib is doing is, it is killing the cancer cells by incapacitating them from repairing their DNA, and simultaneously making them very sensitive to action by immunotherapy. And then we are using pembrolizumab at the same time, which is immunotherapy, and hence we expect these 2 drugs to synergize, and lead to an exponential increase in cancer cell death.

Dr. Shuch: So Neeraj, so it sounds like there's pretty strong scientific rationale. But what question does this study aim to answer? Patients want to live longer? They want to be more stable on therapy?

Dr. Agarwal: The study has 2 major primary endpoints, which basically means 2 major questions the study is asking. Number 1 is, are patients going to live longer when they receive this novel combination versus standard therapy? And secondly, are they going to respond for [a] longer time, meaning they will have a longer duration of disease control defined as the radiographic progression-free survival. That is another primary endpoint of the study. So the study is asking whether patients are living longer, with better control of their disease with this novel combination.

Dr. Shuch: So Neeraj, with this new approach, are there any specific risks that patients would want to know about for this type of study?

Dr. Agarwal: Pembrolizumab is already FDA-approved for more than 10 different kinds of cancers at least. This is an immunotherapy, which basically up-regulates our immune system in a rather non-specific way. Most of the patients, the vast majority of patients take pembrolizumab very well with minimal side effects. But then a small minority of patients, I would say somewhere around 4 to 5 percent, patients have hyper activation of the immune system, which can attack our own organs. So the most common side effects with any immune checkpoint inhibitor like pembrolizumab include diarrhea, liver toxicity, skin toxicity, and less frequently lung toxicity, or attack of immune system on the endocrine glands. These are only some of the toxicities which we usually see on our clinic, but it doesn't mean other rare toxicities may not happen. So these drugs require close monitoring. They're given every 3 weeks. So pembrolizumab, especially, is given every 3 weeks. And it is very important that patients are seen regularly by their oncology providers, so that if there are any of these toxicities are happening, they can be controlled at a much earlier stage, rather than becoming very severe and being picked up at a more severe stage.

So I just want to add the toxicities of olaparib, which is already approved for patients with breast cancer and ovarian cancer. So we are not talking about any experimental drugs here for human beings. Both of these drugs are approved for various cancers already, with very well-defined toxicity profile. The combination is unique. Combination is being tested for the first time. So olaparib can cause bone marrow suppression, which basically means it can lead to anemia, low platelet counts, and low neutrophils, which are the defense cells fighting for us against infection. Most of these toxicities are easily manageable by modifying the dose of olaparib. 

Dr. Shuch: Neeraj, it sounds like this could be a really important study, and we'll keep an eye out for future updates. Please keep us posted. So let's move on to some of the exciting kind of work in bladder cancer. Petros, can you discuss this ongoing study that was presented at ASCO GU, the KEYNOTE-866 protocol? [Perioperative Pembrolizumab (MK-3475) Plus Neoadjuvant Chemotherapy Versus Perioperative Placebo Plus Neoadjuvant Chemotherapy for Cisplatin-eligible Muscle-invasive Bladder Cancer (MIBC) (MK-3475-866/KEYNOTE-866) (KEYNOTE-866)] 

Dr. Grivas: Sure. Before I start, I want to say that I have done consulting with this trial sponsor, which happens to be Merck, for unrelated reasons and not for this trial.  And this trial is open in our institution, but I'm not involved directly into that study. This particular clinical trial is trying to evaluate the following question. Right now, the standard of care for patients who are aiming to go for removal of the bladder—we call this radical cystectomy—is to get chemotherapy with the regimen consisting of gemcitabine and cisplatin combination chemotherapy before cystectomy. We call this pre-operative, before the operation, or neoadjuvant cisplatin-based chemotherapy. And that's a standard of care in patients who are fit enough to tolerate this study, because this study can cause side effects. So the question is, can you now use immunotherapy, in particularly this drug called pembrolizumab, which is activating the immune system, in combination with chemotherapy. So chemotherapy plus, pembrolizumab, as compared to chemotherapy plus placebo before patients get cystectomy, removal of the bladder.

Dr. Shuch: So these are patients who are going to go for surgery?

Dr. Grivas: That is correct. This patient population are those patients who have made a decision to go for removal of the bladder, and we call this, as I mentioned, radical cystectomy. And I mention this because there are some other treatment approaches.

Dr. Shuch: The current standard of care is chemotherapy and then surgery. So what is the problem that the researchers are trying to solve?

Dr. Grivas: The main question is, does the addition of this immunotherapy to chemotherapy increases chance and [the likelihood of] not finding any residual cancer when the bladder is removed, and whether it actually increased the time of being cancer-free and alive down the road. So does the addition of immunotherapy to chemotherapy improves how these patients do over time, in terms of less of cancer recurrence, meaning cancer coming back, and longer life?

Dr. Shuch: Okay. So you want to see the tumors disappear, and then you want to prevent patients from having recurrences with this study.

Dr. Grivas: That is correct, and ideally, live longer, if possible.

Dr. Shuch: And how was it specifically designed? What was the rationale with this type of approach?

Dr. Grivas: Brian, this is an important question because we have to use previous information to inform the design of those trials. And I would mention that there are some observations about chemotherapy and immunotherapy combinations might work well in other cancer types. And particularly, in patients with bladder cancer, there were a few previews, smaller-sized clinical trials that showed promising results, meaning higher chance of making the cancer disappear when they take the bladder out. And because those trials were very promising and also showed that the combination of chemotherapy and immunotherapy was feasible, then the bigger trials now being launched to confirm the results and compare this combination with the standard of care right now. So strong previous data supports this larger trial to evaluate whether this addition makes sense.

Dr. Shuch: So, Petros, patients generally are going to go to surgery. You're giving them a different medication, immune medication. What would be additional risk that patients would have with this approach?

Dr. Grivas: So every time you add a new therapy, there is a chance of side effects as Dr. Agarwal mentioned before. And particularly, when you add immunotherapy, there is a small but real chance of having immunotherapy-related adverse events. And that's what we call side effects from a very activated active immune system. And I think it's important to have this discussion with the patient about benefits or risks before the trial starts. And before the patient makes a decision. Overall, these immunotherapy-related adverse events usually, as I mentioned, are not very common, especially when we compare the immunotherapy with the chemotherapy. However, we have to be very careful, especially with a combination. And these patients are monitored very closely for any side effect that might happen. And I think education is important for both the patient and the medical provider team, how to monitor and do a close observation for those side effects. The side effects of chemotherapy are standard. And that is something that's also a part of the discussion with the patient.

Dr. Shuch: Got it. And is this still open? And when do you think we'll see results for this work?

Dr. Grivas: Yes. The trial is still open. There is a way to go. It started accrual fairly recently, and I think their efforts for accruing patients in multiple cancer centers. So I would definitely consider this clinical trial for patients who are thinking about getting removal of the bladder and who [are well enough to] get chemotherapy, and they can discuss that option with a medical provider because the trial's going to be open at their cancer center or another cancer center. So definitely, it’s open and accruing patients.

Dr. Shuch: I see. It seems very exciting that they're moving this type of therapy to a new space. Petros, keep us posted as this trial progresses.

Dr. Grivas: Thank you. Will do.

Dr. Shuch: So moving on to kidney cancer. Monty, let's discuss this PDIGREE trial. [Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study] Besides obviously having a very interesting name, it seems like it's a pretty novel type of approach. Can you briefly summarize the study and design?

Dr. Pal: Yeah. Thanks, Brian. So the intent of this study is to take patients with advanced kidney cancer—these are folks where the cancer has [spread] beyond the borders of the kidney to the lungs, to the liver etc. All patients receive standard immune-based treatment in the upfront setting. And then a couple of months in, they actually look at the response that they've achieved, and based on that, decide on different lines of treatment beyond that.

Dr. Shuch: So who is the ideal patient for this study? Who is it intended for?

Dr. Pal: Yes. So this particular study, as I've mentioned, is really for those patients with advanced disease. And beyond that, we in the clinic are using different criteria [to assess] how functional a patient is. It's based on their labs, etc., to define whether or not they have what's termed good risk, intermediate risk, or poor risk. And I think as you're looking at treatment options, as a patient with kidney cancer, it's important to figure out which one of those risk criteria you fit into. This particular trial is intended for patients with intermediate and poor risk.

Dr. Shuch: Got it. So these are patients that are newly diagnosed. Correct?

Dr. Pal: Exactly. Exactly.

Dr. Shuch: So what is the current standard of care for these patients? What would you give them outside of this trial?

Dr. Pal: There's a number of options for kidney cancer. When I started in this business, we only had about 2 to 3 treatments for the disease. And now, it's expanded to more than 12 FDA-approved therapies, which is just mind-boggling. Typically, if you're just diagnosed with advanced or metastatic kidney cancer, you'll start with a combination of immune treatments, 2 immune therapies. And that's really the basis of this particular trial. Or you might get a mix of targeted treatment and immune treatment up front.

Dr. Shuch: So Monty, if we have so many exciting therapies, what is the problem that the clinical trial team is trying to solve here?

Dr. Pal: Great question. I think the big issue is that we know that patients who aren't doing well in therapy need to be switched. We know that patients who are doing exceptionally well on therapy can be continued on their current treatment. For the in-betweens, for patients who might have some stability in their tumors, but maybe not the type of shrinkage that we want to see, we really don't know what the best option is. And that's really where the PDIGREE trial comes into play.

Dr. Shuch: So with that in mind, how is it designed to kind of answer that question?

Dr. Pal: So again, we're taking patients who are receiving immune therapy in the upfront setting. We're taking a look at their response at around the 3-month mark. And typically, if you're a patient with kidney cancer, that's how often I would image you with scans. So at the 3-month mark, we look and see. If you've got a complete response—I think it's pretty intuitive—you're just going to continue on immune treatment. If you're actually having a very poor response, meaning the cancer is continuing to grow, it's migrating to new sites, you'll go on to targeted therapy.

On the other hand, if you're in-between, if tumors are maybe shrinking more modestly, or just staying the same size for the most part, that's when you would be randomized to either continue on immune therapy alone, or go on a mix of targeted therapy with immune therapy.

Dr. Shuch: So what is the overall question that the study is hoping to answer? The patients who are getting that additional targeted therapy, what is the hope for them?

Dr. Pal: I think really what we're hoping to see is that those patients actually have delays in their cancer progression. There will be a longer time until they see their cancer grow. Furthermore, we're hoping, actually, that we might improve the survival of these patients.

Dr. Shuch: Got it. So the patients who are starting this therapy, and they have an additional medication, that targeted drug, what would their specific risk be by participating in this study with that drugs?

Dr. Pal: So we've had some great conversations with Dr. Agarwal around the targeted therapy in prostate cancer. He was talking about PARP inhibitors. In kidney cancer, the general principle of targeted therapies are they tend to cut off the blood supply to tumors. But they don't just do it there. They can do it in other organ systems, as well. By virtue of that, you can have a handful of different side effects, including hand-foot syndrome, which is peeling of the skin on the hands and soles of the feet. You can potentially have high blood pressure as a consequence of that mechanism. You can also have diarrhea. These tend to impact the gut. Those tend to be some of the principal side effects. But, of course, I always refer patients to the consent form for these studies for a more exhaustive review.

Dr. Shuch: Got it. But some patients may not have any of these side effects. True?

Dr. Pal: You're absolutely right. It's just amazing to me that I have more than a handful of patients in my practice who experience little or none of these toxicities. Having said that, it's still so important to disclose the possibilities when you're discussing these trials.

Dr. Shuch: Got it. Is this trial still open to patients? And when do you think the results would be available?

Dr. Pal: So at this particular trial is planning to accrue several hundred patients. And we're really in the trial's infancy. We've just had over about 150 patients accrued to date. So there's still ample opportunity to get the study for your patients in practice. And to the patients who are listening to this, it's certainly a trial that I would like you to inquire about at your respective cancer centers. It's open all over the country.

Dr. Shuch: Well, Monty, that seems really fascinating. The idea that it's an adaptable trial, that patients start on therapy, and you see how they do. We'll definitely keep an eye out for that trial in the next few years.

Dr. Pal: Thanks a lot, Brian.

Dr. Shuch: Great. So thanks to our guests. Thank you for tuning into this podcast. I'd like to thank my guests Dr. Neeraj Agarwal, Dr. Petros Grivas, and Dr. Sumanta Pal. There are many types of clinical trials for urologic cancers that are ongoing, all with the shared goal of improving the way we treat these diseases. If you're wondering about participating in a clinical trial that might be right for you, definitely, talk to your healthcare provider. Please tune in next time for further discussions on additional advances in our urologic cancer field. Thank you so much.

ASCO: Thank you, Drs. Shuch, Agarwal, Grivas, and Pal.

Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for.

And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. 

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. 

The beginning of the COVID-19 pandemic brought with it confusion, fear, and uncertainty for most people around the globe. These feelings were often heightened for people with cancer as they experienced disruptions or changes in care, such as following greater safety precautions at their treatment centers, having their appointments shifted to televisits, and facing delays in recommended cancer screenings. 

As a response to the COVID-19 pandemic, Cancer.Net developed several resources for people with cancer, including its post “Coronavirus and COVID-19: What People With Cancer Need to Know,” written by Dr. Merry Jennifer Markham. After publishing this post on March 3, 2020, Dr. Markham reviewed and updated the post for 650 days straight to make sure people with cancer were receiving the most up-to-date and relevant information about COVID-19. The post went on to receive the Award of Distinction from the eHealthcare Awards in the Best COVID-19 Pandemic Related Communications category and was translated into Spanish, Portuguese, Russian, and Arabic. 

In this podcast, ASCO’s Chief Medical Officer, Dr. Julie Gralow talks with Dr. Markham about her role in creating information for people with cancer throughout the pandemic, how the pandemic has shifted her perspective, and where she sees the future of the pandemic response headed.

Dr. Gralow: Hello. I'm Dr. Julie Gralow, ASCO's Chief Medical Officer. Today, I'm talking with Dr. Merry Jennifer Markham, an ASCO volunteer and the Cancer.Net Associate Editor for Gynecologic Cancers. Cancer.Net is the patient information website of ASCO. Dr. Markham is also chief of the University of Florida, Division of Hematology and Oncology, a clinical professor in the University of Florida College of Medicine, and the associate director for medical affairs at the University of Florida Health Cancer Center.

Dr. Markham played a key role in ensuring that ASCO provides up-to-date information about COVID-19 for patients, survivors, and caregivers through Cancer.Net. Since March 2020, she devoted a remarkable amount of time and energy to this endeavor, including a stretch of 650 straight days of reviewing and updating our patient information about coronavirus. Wow. That's true dedication, Merry Jennifer. So I would like to kick it off to you, Merry Jennifer. First of all, thank you so much for everything you've done during these past couple of years in keeping our Cancer.Net website up to date for patients during these incredibly challenging times. I'm looking forward to having a conversation with you about all of this.

Dr. Markham: Thank you so much. It's been an honor and a pleasure. And the Cancer.Net team has been just fantastic to work with.

Dr. Gralow: Great. Glad to hear it. So Merry Jennifer, when you suggested that ASCO provide some patient-focused content on COVID and cancer, did you think we'd still be talking about this 2 years later?

Dr. Markham: Oh, I had no idea what to expect. No. I think I, like many of us, thought that this would be a very time-limited event and maybe by the Christmas time of 2020, that we would be done. We were all, of course, disappointed to learn that that was not how a pandemic plays out, but I definitely had no idea what my one email to the group would lead to.

Dr. Gralow: What do you remember about March of 2020?

Dr. Markham: It was a really scary time and a very uncertain time. None of us really knew what was going to come. We were watching how the pandemic or just the viral infection was playing out at the time in other countries, but really, we're not sure what was going to happen to our patients. And I was coming off a stint, I believe - the timing is a bit of a blur - on the communications committee for ASCO. And communications is something that I am passionate about, cancer communication with patients and with other colleagues. And I recall being in clinic and answering questions from patients. And really, it felt like there needed to be some broader level of communication that our patients could refer to you but also colleagues and people around the world. That's what I remember. And I remember reaching out and saying, "Hey, I wonder if maybe ASCO should do something." I didn't intend to volunteer myself to do something, but somebody needed to jump in, and I was ready.

Dr. Gralow: Well, I was still practicing at the time, and I know all the different questions that we were getting. It was such a confusing time. We didn't have information. It was changing on a daily basis. I'm impressed that you thought that we were going to be dealing with this maybe even until the end of 2020 because I was thinking, "Oh, 3 or 4 weeks. We can all quarantine for 3 or 4 weeks. Right?" And here we are more than 2 years later. So you worked on the content for 650 days straight. I mean, every single day for 650 days, you looked to make sure that what we had on there was accurate, and now we backed off a little. But you're still looking at the content a couple of times a week. How has that level of focus on COVID-19 affected your perception and experience of the pandemic?

Dr. Markham In the very beginning, the content was really updated daily. I think something was changing on a daily basis. And so it became part of my morning habit, first thing in the morning with a cup of coffee if I had time for that, to read whatever was happening in the news that day and just paying attention to where we were headed, knowing that there would be changes. In the beginning, there was not enough masks, so we weren't recommending everyone “Go out and buy surgical masks." And then the policies changed on that as we had plenty of masks and then, of course, vaccines and so on and so forth.

I think I felt, like many people, a loss of control when the pandemic happened. Right? I think that so many people felt the sense of loss and the sense of uncertainty. And it reminded me actually of what patients with cancer probably experience with a new diagnosis, the sense of loss and uncertainty for what the future holds. And I think like many of my patients who really want to dive in deep to the research of their own cancer and treatment course, it actually gave me a sense of comfort to delve deep into the facts of what we were learning on a daily basis about COVID. Having that knowledge at my fingertips and being able to put it into layman's terms really did help me, I think, not become emotionally tied up in all of the sadness of the pandemic and the loss of travel and the loss of being able to be with loved ones. So for me, it was a little bit of a coping mechanism, I think. I didn't realize that at the time, but in hindsight, I really think it was.

Dr. Gralow: So becoming a true expert in COVID and cancer was your coping mechanism. That's interesting because you were the leading authority here on what everyone was recommending. Do you have any particular moments, good or bad, that really stand out for you from those early days?

Dr. Markham: I think what stands out the most is we focus so much on science as practitioners of oncology and in these health professions and as scientists. And I remember being very disappointed and hurt whenever I encountered someone, whether it was a patient or a family member or a colleague or-- not colleague but acquaintance, perhaps, who didn't believe that this was a real thing. And I was really pouring my heart and soul into the work of providing patient education on this and trying to do the same in my own clinic and with my own family members. And to have people brush it off as a non-thing, it was hurtful, and it was also just very disappointing as a physician and scientist.

Dr. Gralow: And things were changing fast. Now, you yourself ended up with a COVID diagnosis at the end of 2021. Did that personal experience change the way you viewed ASCO's roles in supporting people with cancer throughout the pandemic?

Dr. Markham: So I was minimally symptomatic, which was really thanks to science and thanks to the vaccines and having boosters. So number 1, it was very mild. But like many people who have a diagnosis that's new to them, I was nervous. And so I did feel reassured, though, because I had a pretty good understanding of what was happening and what was going to happen, and I knew that I was protected because of the vaccine and boosters. But it can be a scary time, and I think that it just gave me a little more insight into what people who I've taken care of, who have cancer and then have experienced a COVID diagnosis, have felt. Unlike my patients with cancer, I'm not immunocompromised, so I felt pretty comfortable. But it can certainly be scary. And I did have that appreciation for-- not just the infection but having to isolate myself from my family, I think that really was the hardest part and the inconvenience of it.

Dr. Gralow: Well, I'm glad you just had a mild case, and hopefully, you have no residual symptoms. But it is interesting when you have, either within your family or yourself, a personal confrontation, either with COVID or with cancer, that it gives you a different perspective.

Dr. Markham: Absolutely. That is so true.

Dr. Gralow: So we're now 2-plus years into the pandemic. I know you don't have a crystal ball, and I know we've thought we were on the downswing and things picked up again. But where do you see this going? I mean, not just COVID itself but public health, immunizations, the whole pandemic awareness. Where do you see this going in the U.S. and worldwide? We've had the flu coming around every season. We didn't wear masks. We have vaccines. Not everybody got vaccines. What are we going to learn from all of this, and where do you see the future will be?

Dr. Markham: I think that one of the major learning experiences that all of us who are in medicine and health care and those in health communication and health policy-- what we have learned is that science communication really does matter, and it's hard to do it in a very rapid-fire pace and do it well. But I think we've all seen examples of how communication around factual data and removing misinformation is actually critical. I would love to see this pandemic go away, but I think that what we've seen over the last couple of years with the new variants coming out, it's clear that we're not going to have 99% of our population vaccinated. I think, really, on all fronts, vaccination uptake is not that high. So there will be people who are either unable or unwilling or who will defer getting vaccinated. And unfortunately, this will lead to these waves of new variants coming like the current variant that is circulating. But I do think that there is hope.

One of the reasons that a lot of my patients delayed getting vaccines in the beginning-- many of mine did, but there were some holdouts who really were not comfortable getting vaccinated. There is now more time. And so we do have more safety data, and we know that the vaccinations are safe against-- the COVID vaccinations are safe. So I think that I have seen more patients in those last 6 months become vaccinated. They were holdouts initially, and now more are doing it. And I'm hopeful that this trend will continue. I do think there are pockets where we are seeing vaccination rates start to pick up again. I don't know. I'm happy to keep reviewing content, though, and updating. The updates have become a little less frequent, which is great. I love when our focus on updating is really on new therapies and new vaccines and new vaccine sequences and schedules. So I think we're in a fairly stable place - knock on wood - right now.

Dr. Gralow: In our immunocompromised population, which is only a subset of all of our patients with cancer, do you think we'll see more mask wearing in the future?

Dr. Markham: I do. I do think that actually this is one area where we, as a culture, have probably begun to shift in the United States and especially among people who have a personal risk or a family member with a risk factor that might increase their chances of severe COVID. Just a personal anecdote. I traveled internationally for the first time since COVID a couple of weeks ago, and my entire family, all vaccinated and boosted, wore our masks, as it's the federal requirement to do so on planes. However, we landed in an international location where that was not a requirement. None of us wanted to take our masks off. We felt more comfortable, and I saw a lot of people who also remained masked even though it was not a requirement. So I do think there's a shift in this culture. I'm as tired of the masks as anyone, but it really does have a protective measure and is, I think, important, especially for our patients who have a weakened immune system or other medical risk factors for developing COVID or other infectious diseases.

Dr. Gralow: So kind of in closing, you did such tremendous work for ASCO, for our patients with these regular updates. But what's the experience meant to you as an ASCO member and a member of the oncology community?

Dr. Markham: I joined ASCO when I was a fellow, and I was taught the importance of our organization by my faculty members and my mentors. And as soon as I realized I could, I volunteered to serve on ASCO committees and task forces. And it has been one of the most rewarding parts of my career. And it's something that I encourage junior faculty and fellows to do as well. ASCO is such a leading voice. It is the leading voice for oncology care globally. And just the opportunity to contribute something back has really meant the world to me. It's been an honor to be able to do this work.

Dr. Gralow: Well, on behalf of ASCO, I want to thank you again for all of your commitment to this. We're thrilled to have you as a volunteer, and we will continue to call on you as a volunteer. Really appreciate that. And I do know that throughout the COVID-19 pandemic, a lot of what ASCO was posting, a lot of the webinars we had, etc., were being used around the world. And you contributed majorly to that as well. So for that, I thank you. And I thank all of our listeners. This has been Julie Gralow and Merry Jennifer Markham talking about our Cancer.Net COVID-19 information that Merry Jennifer tirelessly led daily, essentially, for a couple of years. So thank you so much for that. It's been great talking to you.

Dr. Markham: Thank you.

ASCO: Thank you, Dr. Gralow and Dr. Markham. Find all of Cancer.Net’s resources on COVID-19 and cancer at www.cancer.net/covid19.

Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.  

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. 

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate. 

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

In this podcast, Dr. Lidia Schapira and Dr. Daniel Mulrooney discuss a study published in the Journal of Clinical Oncology about mental health outcomes for AYA cancer survivors and how young survivors can get the mental health support they need after cancer.

Dr. Schapira is Associate Professor of Medicine at Stanford University School of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute. She is also the Cancer.Net Editor in Chief. Dr. Mulrooney is an Associate Member in the Division of Cancer Survivorship at St. Jude Children’s Research Hospital. He is also the Cancer.Net Associate Editor for Pediatric Cancers.

View disclosures for Dr. Schapira and Dr. Mulrooney at Cancer.Net.

Dr. Schapira: Welcome to this Cancer.Net podcast. I'm Lidia Schapira, the editor-in-chief, and with me today is Dr. Dan Mulrooney, an expert in cancer survivorship in children's cancer. Welcome, Dan.

Dr. Mulrooney: Thank you, Lidia. Nice to be here.

Dr. Schapira: We have no disclosures for this podcast. And the article that was just published in JCO by Dr. De is what has prompted this conversation with Dan. In that article, scientists from Canada were interested in looking at the incidence and predictors of mental health outcomes among cancer survivors, of adolescent and young adult cancers. So they used a large database, and they looked at what happened to those adults who were diagnosed when they were between 15 and 21 years of age and had survived at least 5 years since their cancer. So they were now adults. What they were interested in were the mental health episodes that were either outpatient mental health problems, mostly anxiety, that were diagnosed in these cancer survivors and also, severe psychiatric episodes such as hospitalizations for a disease called schizophrenia and other important psychiatric illnesses. And they compared them to adults that were matched but did not have a history of cancer. And surprisingly, perhaps, or not so surprisingly, and this is what we'll discuss, they found that the survivors of cancer had more mental health problems. So there was a 30% higher rate of outpatient mental health visits, mostly for anxiety, and a 20% increased risk of a severe psychiatric episode as compared to these matched controls. So, Dan, I first wanted to get your reaction to this, and please feel free to correct my analysis if your interpretation was slightly different.

Dr. Mulrooney: No, it really isn't. Thank you, Lidia. It's a really important article concentrating on a group of survivors that we really already know are at higher risk for adverse mental health outcomes and psychosocial risks following their cancer therapy. But what's so interesting is they were able to combine large data sets. They were able to compare these survivors to the general population, which is very relevant for health care providers taking care of these patients in the community. And in addition to that, what I thought was particularly interesting is their ability to look at both outpatient visits and those more severe mental health issues that require an emergency room visit or require admission to the hospital. I think this is very informative information about this high-risk group of survivors and hopefully will be instructive if we can interpret this and turn this into services that we can direct to these patients.

Dr. Schapira: I found it interesting, Dan, also that they said that they only captured the mental health visits in the outpatient setting that were delivered by physicians because of the data. So, in fact, visits with social workers or psychologists did not even make it into these statistics. And that suggests to me that there may be even more problems that were not captured by these numbers.

Dr. Mulrooney: I think you're absolutely correct on that. If anything, these numbers are an underestimate of the issues and the problems that may be out there. It's only those that made an appointment and went to a mental health care provider. They missed social workers. They missed other social networks, ministers, religious organizations that might be providing help as well. And of course, we're talking about a young adult population that may not always reach out for these services. And so, this group did reach out. So we probably have the more severe group represented here, but we're missing a large population underneath this. I suspect you're absolutely right.

Dr. Schapira: And so, if we think about what we can do with his information, how we can think about guidelines, assessments, and support, let's think back to when these young adults and adolescents are first diagnosed. I was also struck by the fact that there was a difference with more mental health problems in those treated in adult cancer centers than those that were treated in pediatric cancer centers. Can you tell me what may account for those differences?

Dr. Mulrooney: That's a very interesting question and fact that came out of this paper. And I suspect there are probably a number of reasons. I think globally, this paper looks at mental health issues in cancer survivors, which we have to separate from mental health issues in patients going through active cancer therapy. There may be quite a bit of overlap. There may be some similarities. But I suspect, particularly in the AYA population, the issues that they encounter as a survivor are different than those that they struggled with maybe as a patient. And they saw this difference, particularly for outpatient visits, based on where they were treated. One thing to point out is the majority of these survivors were actually treated in the adult cancer centers. Because in Canada, if you're over age 18, you're considered an adult and you're treated at an adult cancer center. So there was a smaller population, I think it was only about 25% to 27%, that were actually treated in pediatrics. And certainly, the focus and the culture of care is different between pediatrics and adult medicine. And I suspect there may be some differences in survivorship support and care. And these survivors, they were relatively soon after receiving their care and those in the pediatric community are probably receiving, I suspect, maybe more follow-up, a survivorship program, probably a little bit more structured, and hopefully a survivorship program that has social work support or psychosocial services provided. Now, I can't say that the adult centers don't have that, but of course, the population is much larger, and the visits and that culture is very different than they receive in pediatrics. So it is possible that some of those early services and supports are just not available to that population.

Dr. Schapira: So let me pick your brain about this a little bit since you are immersed in this world. What does it take in your mind to create the best possible environment for these young adults to thrive after cancer or to have an opportunity to receive all the mental health support that they need in order to move on with their lives?

Dr. Mulrooney: I think number 1 is to recognize it as an issue. In particular, we know that this AYA population is considered a high-risk population for mental health issues after cancer. And so number 1, we really need to recognize that. And this paper draws our attention to that very nicely, that it is an issue, there's a high prevalence of mental health issues after cancer therapy. But in our survivorship clinics, we need to address the medical and chronic health concerns after cancer therapy, but we can't forget these psychosocial issues. And how does that affect this individual survivor? They're struggling with lots of issues after cancer: fear of recurrence, fear of a second cancer, maybe body image issues, maybe health conditions that their peers at this age are not encountering. And so in addition to treating those and doing appropriate surveillance, we should really also be doing mental health surveillance and screening, and identifying appropriate referrals for them to address those issues.

Dr. Schapira: So, Dan, how do people like us who are not trained in mental health, what should we be doing and thinking about as oncologists or even as primary care physicians who see these patients? What can we do?

Dr. Mulrooney: Yeah, I thought a great deal about that when reading this because even in primary care, there's at least some general screening for mental health or depression. Most primary care providers, at least mine, hands me a little questionnaire that I fill out while I'm in the waiting room. Obviously we need to do that, but perhaps we need to take it a step further in this unique population, to maybe ask the appropriate questions in a survivorship clinic. Hopefully, we have social work support. Not all centers will have that. Obviously, there's going to be access issues. And in the United States here, there's probably financial issues that maybe didn't occur here in Canada. But we really need to advocate for taking those questions a little bit further, digging a little bit deeper, and really having a social worker available, maybe to do that screening in person, maybe not do it on paper in a group that we know is high risk.

Dr. Schapira: So that was 1 of the things that I also thought about as I was reading this, this idea that screening tools are great, when you think that what you're screening for has a relatively low prevalence. But if, in fact, this is so important, maybe an assessment done by a professional who's trained may actually take us a little bit further and help us so that we don't miss people. I know many screening efforts, for instance, where the data is captured, but then there is no link to a solution or a referral. And it's not that people don't mean well, but there are all sorts of reasons why things fall through the cracks, which is sad. Whereas if there were a relationship and an assessment done by a professional, I feel then we would be more-- our default would be more to ask, to support, and to keep asking. Because 1 of the things I think the authors also tell us is, you need to keep doing this over the course of many years. Is that your understanding as well?

Dr. Mulrooney: Absolutely. All of us were trained as oncologists, and we feel like we maybe don't have the skills to address this. But we certainly have the ability to ask and delve a little bit deeper. We know how to take a history, we know how to-- we take care of patients in very critical realms. And so we certainly are comfortable asking difficult questions. And mental health questions should be really no different from that. And, an important thing I noticed in this paper is 1 of the predictors of a mental health issue for the survivors was a preceding mental health issue even before diagnosis or going through therapy. So are we missing them all the way along? And maybe we should be intervening or addressing this when they’re our patients in our cancer center, and then not miss that transition to appropriate survivorship care, and appropriate psychosocial care after that.

Dr. Schapira: I couldn't agree with you more. I think between the 2 of us, we could design the perfect cancer care system, right, where we reach out to these adolescents and young adults. And, in some cases, I imagine in the younger ones, there's also the parents to consider at the time that they're getting treated, right? And then maybe those relationships as they grow into adulthood also change. And there may be, sort of, a disruption in what we think of as the family unit or the supports available to that young person so it's very complicated. Do you have any advice, given the work that you do in this survivorship clinic that you've had, how can we even begin to do this? To reach out to everybody and make sure that people feel connected to you, but then also that when you let them go, that they can find the support they need?

Dr. Mulrooney: What a struggle it is, particularly with these young people who are growing into their own, becoming more independent, want to take more responsibility, but then are struggling with so many of these health care issues, whether they're physical or mental. And family support and the family unit has to be considered, particularly with the younger population. And not only the mental health of the survivor, but the mental health of the parents or the family who may have their own issues preceding cancer therapy, or may be struggling with how to take care of my child after cancer, or this fear of recurrence themselves. And oftentimes the parents may have a harder time than the young person does. And we have seen both, post-traumatic stress disorder, but also post-traumatic resilience in some of these patients. They really feel they've come through something and it's made them stronger and it's changed their outlook on life. In our clinic, we make sure that we at least have them see a social worker when they come into the survivorship clinic, and then again, as there may be mid-adolescence and a year or 2 before they're going to graduate or leave our care. So that we're addressing those issues or identifying those issues. And then that gives us at least a year or 2 to try to find the services locally, wherever they live, for them. The handoff in that transition is very difficult. And I won't lie, I've been concerned about the transition for a long time, as you know. I think it's an area we really need to improve upon. We need more buy-in from the medical community across the board, maybe more research in that area.

It's a real struggle, but we can't just finish their survivorship care and not make sure that they're not connected again locally because the care continues, and the paper showed that that the risk continued to increase and went up with time from diagnosis. So it's a real struggle, it's just really hard.

Dr. Schapira: You just described the challenge that we all face so beautifully. And so, my final question to you is about your experience with young cancer survivors during this last year, with the COVID pandemic. With the isolation and all of the mental health issues that we've heard about just among young people in general, what have you found? I imagine you're going to tell me that there is enormous variation, but I'd love to have you share with our listeners a little bit of what you've learned.

Dr. Mulrooney: It has increased the stress on cancer survivors, and it's made-- the pandemic's made life difficult for everybody. But again, now if we're talking about a population who has survived cancer, who may have some chronic health effects related to that, and they've called us and they said, "Am I at increased risk? What should I do? Do I need to do something different to protect myself?" And so far, we don't know. The data really aren't mature enough to understand if a survivor of cancer is at a higher risk than somebody in the general community. Certainly, if they're on immunosuppressive medications or certainly if they have chronic health conditions, we suspect they're at higher risk, just as you might see in the community, but particularly with an older population.

Access to care is certainly more limited, and so issues, just as we're talking about here, mental health services are magnified, and it's harder to reach out and get those services. I was thinking a great deal about that when reading this because, in some ways, they may be able to get services a little bit more quickly because it's all being done by telehealth, and these encounters are probably not being done in person. On the other hand, it's disrupted scheduling and access. So, again, I worry that there's a large population that was missed even in this study, but a large population now that's being missed and not receiving services because of the pandemic. Hopefully, as this begins to ease, we can start attacking that problem and getting to more and more of those people.

Dr. Schapira: Are there resources for survivors, especially now in the time of the pandemic, someplace they can turn to if they want to learn more about this topic?

Dr. Mulrooney: There are a number of resources, and particularly with the Children's Oncology Group, has developed what they call Health Links and documents in lay language that can be a resource for survivors who are struggling with physical illness and also mental health illness. The website is called survivorshipguidelines.org, and the link is to the Health Links on that page. There's a Health Link particularly for mental health issues following cancer, and also 1 for issues related to the COVID pandemic that I hope survivors might find helpful.

Dr. Schapira: Well, thanks, Dan, it's been lovely chatting with you. It always is. I know I've learned a lot and I hope this is useful to our listeners as well. Thanks for everything and thanks for all you do every day.

Dr. Mulrooney: Thank you very much. It was nice to be here.

ASCO: Thank you, Dr. Schapira and Dr. Mulrooney. Find more resources for young adults at www.cancer.net/aya. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

 [music]

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

Greg Guthrie: Hi everyone, I'm Greg Guthrie, a member of ASCO's patient education content team, and I'll be your host for today's podcast. ASCO is the American Society of Clinical Oncology, and we're the world's leading professional organization for physicians and oncology professionals caring for people with cancer. Today we're going to be talking about what patients should know about cannabis, cannabinoids, and cancer. ASCO recently published a clinical practice guideline on cannabis and cannabinoids for adults with cancer.

I'm happy to have 2 of the co-chairs from the committee that developed this guideline as our guests today. Dr. Ilana Braun is an associate professor at Harvard Medical School. Thanks for joining us, Dr. Braun.

Dr. Ilana Braun: Thanks so much for having me.

Greg Guthrie: It's a pleasure to have you here today. And Dr. Eric Roeland is an associate professor of medicine at Oregon Health and Science University. Welcome Dr. Roeland.

Dr. Eric Roeland: Thanks, Greg.

Greg Guthrie

Great. So before we begin, I want to note that neither Dr. Braun nor Dr. Roeland have any relationships to disclose related to this podcast, but you can find their full disclosures in this podcast's show notes.

So let's start with the fundamental question about this discussion, and that is what is a clinical practice guideline and how does it help guide cancer care? Dr. Roeland, can you start with this?

Dr. Eric Roeland: Of course, yeah. A clinical practice guideline describes the best practices or what clinicians call the “standard of care” with regard to a specific topic. So this is kind of the blueprint that clinicians use to guide their practice when taking care of people with cancer. And the American Society of Clinical Oncology clinical practice guideline on the use of cannabis and/or cannabinoids summarizes the best available data collected specifically from humans in clinical trials, and we combined that with a multi-disciplinary panel of expert opinion.

Greg Guthrie: Yeah, I think it's really important to always remember that best evidence comes from research in humans as well as from clinical expertise. So it's the best recommendations that we can have to support cancer care.

Dr. Eric Roeland: Greg, I also think it's very important to understand that there are different places that we gain knowledge in research. One is specifically when we are trying to figure out how a drug works, and we will test that in what we call “preclinical models,” which is usually within animals. And then, once we’ve determined safety and efficacy, then we start taking that information and approach studies in humans. And so when our listeners are learning about new data in the use of cannabis or cannabinoids, I encourage everyone to always stop and ask, is this data coming from the animals or is this from humans?

Greg Guthrie: That's such an important point. And I think it's so essential to always look for that piece of evidence whenever you're reading about scientific advances. Alright, so let's take a moment to talk about what it means when we say cannabis and cannabinoids. Dr. Braun?

Dr. Ilana Braun: Cannabis, which is better known as marijuana, is a plant that humans have turned to for thousands of years as a medicine, in manufacturing—for instance, in the making of rope­—and for enjoyment.

It's often mistakenly viewed as having one main ingredient, tetrahydrocannabinol, or THC, but it actually has more than 300 ingredients that act in the body. Some of those ingredients are referred to as cannabinoids. There are 2 cannabinoids of greatest interest, THC, which I just mentioned, and CBD, cannabidiol. THC is responsible for the high feeling some people experience with cannabis. CBD is not.

Currently in the U.S., some cannabis products containing these cannabinoids can be sourced at the pharmacy, others at cannabis dispensaries, and some through more informal means.

Greg Guthrie: That's great. Thank you for that definition here as we continue this discussion. So what do people with cancer typically think cannabis and cannabinoids will do to help them? Dr. Roeland?

Dr. Eric Roeland: Well, it's a great question, Greg, because in clinic, when patients and their loved ones express interest in either starting cannabis or cannabinoids or are currently using them, I always want to explore what their goal of use is. And interestingly, the goals of use are far-reaching. And I have heard everything from, to help with everything, to cure my cancer. And so it's incredibly important to understand why people are reaching towards these products, to understand what their goals are. If they're focused on using this to treat the underlying cancer, or instead of standard cancer therapies, we have grave concerns about this approach. And it may lead to worse outcomes of your cancer.

However, if cannabis or cannabinoids are being used to help with controlling some symptoms during their cancer treatment, it may be helpful. And especially in one particular case where people have really bad nausea and vomiting that persists despite our best medicines to prevent it.

Greg Guthrie: Thank you for that, Dr. Roeland. Dr. Braun, did you have anything to add?

Dr. Ilana Braun: Maybe I will just point out that decisions on what to target with cannabis are often made through trial and error or in consultation with dispensaries, but not as much as I would prefer in consultation with clinical teams.

Dr. Eric Roeland: So I would also add that it's incredibly important to bring these topics up with your clinical team because although cannabis and cannabinoids are considered safe by many because they're quote “natural,” it's important to recognize that they actually can interact with many of the other medications that you're already taking.

For example, patients with cancer might be experiencing really bad pain or anxiety and taking things like opioids or benzodiazepines. And when you combine that with cannabis, it can prolong some of the effects of sedation or confusion. I'd also like to point out that this is not a time where people want to try cannabis for the first time, when they are weak and/or experiencing poor appetite and higher risk of falls. This is not the best time to be trying cannabis or cannabinoids without clear guidance from the clinical care team.

Greg Guthrie: Do you find in writing this guideline and through your clinical experience that most people who are asking about cannabis and cannabinoids, that they already have been trying to use it or are considering it? Because there's a difference there, right? What goal are they looking for, and do they already have a predetermined assumption about what's going to happen with these?

Dr. Eric Roeland: You know, Greg, as clinicians, we talk about a lot of hard stuff. We talk about challenges in terms of health care, access to care, cultural differences, financial toxicity. And it's so fascinating to me that we don't talk about something as simple as whether or not patients are using cannabis. And the reality is that when patients actually bring it up in clinic, I would say that most times they're already using it and are just simply asking for some advice on how to use it safely and effectively. So once I decided to lean in on this topic and create a space for patients and their loved ones to bring it up in clinic, I have found that it's brought up during most clinical encounters.

Greg Guthrie: Fascinating. And so that's likely why the first recommendation of this guideline addresses the importance of communication between doctors and patients on this topic, correct?

Dr. Eric Roeland: Yes, absolutely. I think that doctors are reticent to talk about this topic because of concerns around legal issues, which can be highly varied across the country. And Dr. Braun can speak to this more.

Dr. Ilana Braun: Yeah, so in order to offer the very best care possible, I think that medical teams should know about all the medicines and supplements a person is taking. And this includes cannabis and cannabinoid products. Why? Well, because, as Dr. Roeland mentioned, cannabis and cannabinoids can sometimes decrease the effectiveness of some therapies that a person is on, likely including some cancer treatments, and they can also worsen side effects of other therapies. And then at the same time, cannabis and cannabinoids can be helpful in managing some symptoms of cancer and side effects of cancer treatment. So using them involves a careful weighing of risks and benefits.

So for these reasons, oncology teams really do want to be part of the conversation as someone thinks through decisions around cannabis and cannabinoids. The ASCO guidelines encourage clinicians to be open and non-judgmental and welcome transparent discussions with patients about cannabis and cannabinoids. From there, clinicians should either assist personally if they feel qualified to do so, or refer a patient to high-quality information or an advisor with greater expertise.

As for the types of information that might be helpful to share with the clinical team, a person with cancer who consumes cannabis or cannabinoids might wish to share why they're turning to cannabis, where they get their products, the active ingredients in them—so is it mainly THC or is it mainly CBD­—how they consume them, are they smoking, are they vaporizing, are they taking them by mouth, how often they consume them, what do they experience as the benefits and risks of using cannabis and cannabinoid products? Their clinicians may wish to know whether or not the cannabis products are being used as an add-on to standard treatments or whether they're being used in the place of standard treatments. And as Dr. Roeland suggested, they probably will want to know how much this practice is costing the patient each month and whether it is affordable.

I think it's especially important to speak with your clinical team if you are considering using high-potency cannabis paste in an attempt to treat cancer itself. So not just manage symptoms, but actually treat cancer itself. The reason I think it's so important to share with your cancer team is that these cannabis pastes tend to have very, very high concentrations of THC and sometimes even CBD. And I think your cancer team can be helpful in thinking through the risks and benefits of that, helping to monitor side effects that might arise.

It is commonly the case that people feel a little bit of confusion with very high doses of oral THC.

Dr. Eric Roeland: I absolutely agree. And I think these high doses of cannabis products, they're often a tincture and delivered in a syringe. And it might look like black tar. And people are told to start off with the dosing of a grain of rice. But then they're told that the dose to treat their underlying cancer can be higher than a gram of cannabis a day. In some places it's a gram and a half. This is very high dosing, and it's going to cause people to feel extremely fatigued and increase the risk of falls and being sent to the emergency department. So I want to warn people about this practice in particular, because it can cause harm. We have no evidence that it actually works.

Greg Guthrie: Thanks for that information there. I was wondering, is there a certain person on the health care team that patients should consider talking to, or anyone?

Dr. Ilana Braun: I think anyone. Health care teams keep in close contact with each other. And so this kind of information would be shared amongst the team. So lots of cancer patients begin by sharing with their infusion nurse or their nurse practitioner. They don't even need to share necessarily with their oncologist as a first step. And anyone on the team should, after these guidelines, be able to access high-quality information through their institutions.

Dr. Eric Roeland: And for those patients who might be in a location where they don't have access to an expert or don't have access to educational resources, I think one of the strengths of this current guideline is that we include an appendix, which clinicians can actually use as a 1-page handout for patients and caregivers to answer some of these most basic questions.

For example, I think there's a lot of misunderstanding about how to take cannabis or cannabinoids. And what we do see is there's a big difference between ingesting orally an edible versus smoking or inhaling cannabis. And so, for example, cannabis when eaten by mouth can take up to 2 hours to have its peak effect. And unfortunately, what happens is that patients won't feel anything after several minutes to a half hour and then stack doses to the point that they get a much higher dose than they really need. And so we really encourage people to be aware of, if it's an edible, that it can take up to 2 hours. Whereas with your breathing it in or vaping, the effects can happen almost right away.

But again, it's important to recognize that cannabis, whether it's smoked, vaped, or ingested, can be in your body for up to 12 hours and may even impact your ability to drive. So it's important that if you are going to use these tools in combination with the rest of your medicines, it's important to do it in a safe way.

Another product that is now available, even over the counter at many grocery stores, is cannabidiol, or CBD. CBD in its pure form doesn't have the euphoria associated with products that contain more THC. Most people are using this as an anti-inflammatory, or targeting sleep.

I would like to recognize that in our review of the literature, we discovered that high doses, meaning more than 300 milligrams of cannabidiol a day, actually changed the measurable enzyme levels of the liver. These enzyme levels in the liver are the same levels that we use to determine whether or not you can get your chemotherapy. So you want to make sure that you're not taking excessive doses of cannabidiol, meaning more than 300 milligrams a day, because you don't want your chemotherapy delayed because your liver enzymes might be elevated falsely from the use of high doses of cannabidiol.

Greg Guthrie: That's great, Dr. Roeland. Thanks for adding that. As an additive or part of the cancer care plan, like with all medications, we need to be aware of what we're taking and report to our health care team so we can watch for interactions and potential side effects, right?

So what are the rest of ASCO's guideline recommendations when it comes to this guideline for cannabis and cannabinoids?

Dr. Ilana Braun: So as a committee, we submitted cannabis and cannabinoids to the same level of rigorous scrutiny that we would any other aspect of oncologic care.

I can think of few other ways to validate this area of oncology science than to do so. And after an in-depth evaluation, the ASCO committee concluded that of all the reasons that a cancer patient might medicate with cannabis, the best scientific evidence supports using cannabis or cannabinoids to help with nausea and vomiting caused by cancer drugs when standard medications for nausea and vomiting don’t work well enough.

Of note, ASCO guidelines make clear that there isn't evidence to hang our hats on that cannabis and cannabinoids can treat cancer itself. What's more, early evidence suggests that cannabis and cannabinoids may actually worsen outcomes for people taking a cancer treatment called “immunotherapy.” Gold-standard clinical trials are necessary to confirm these worrisome findings, but for the time being, people on immunotherapy should probably best avoid cannabis and cannabinoids. I think Dr. Roeland and I and the rest of the committee have hope that more scientifically proven indications will emerge as cannabis research progresses.

Dr. Eric Roeland: Dr. Braun has also pointed out to me that there's literature and evidence supporting the use of cannabis and/or cannabinoids for the management of chronic pain not related to cancer. And this has been actually described in other guidelines, and we need to recognize that our patients living with cancer often have chronic pain that may even predate their cancer experience. However, we do not have strong evidence to support that the use of cannabis and/or cannabinoids helps with cancer pain, which is a common reason that people are reaching for these medicines.

Greg Guthrie: Great, thank you, Dr. Roeland. Thank you, Dr. Braun. So this guideline also recommends the use of cannabis or cannabinoids mainly within the setting of a clinical trial, and why is that?

Dr. Eric Roeland: Well, Greg, I think it's incredibly important for people living with cancer and their loved ones to recognize that access to cannabis has far outpaced our ability to validate and study the best methods of using cannabis and cannabinoids in people living with cancer. Meaning access has far outpaced the science that supports its use. We also recognize that just because something is quote, “natural,” doesn't necessarily mean it is also safe, especially in combination with many of the drugs and cancer therapies that patients must receive while they're on treatment.

Therefore, for those of you very frustrated by the lack of evidence to support the use of these medicines in people living with cancer, you should be the first in line to volunteer for any studies that help us collect prospective evidence to demonstrate not only safety but efficacy.

I would also like to recognize how challenging it can be to perform these types of clinical trials based off of the formal designation by the federal government classifying this—cannabis and/or cannabinoids—as a Schedule 1 medicine, which creates multiple barriers for those clinical researchers who want to fully describe the safety and efficacy of these drugs. Therefore, if there is someone near you who is doing clinical research in this space, we greatly would appreciate your involvement in those clinical trials.

Dr. Ilana Braun: I agree with Eric. By participating in clinical trials, a person is doing a very kind thing for others, helping to advance the science behind cannabis and cannabinoids. Only through this controlled, systematic testing will the medical community understand whether cannabis and cannabinoids can be helpful for indications beyond the chemotherapy-related nausea and vomiting.

And we as a society need to understand whether cannabis or cannabinoids can be helpful for cancer pain, for cancer-related poor appetite, to name just a few. These clinical trials will help us move the field forward. And in terms of personal benefit, I could imagine that clinical trials might offer someone more quality-assured cannabis products, more scientifically based dosing guidelines, careful clinical observation should side effects present, and potentially efficacy. But of course there are no guarantees. That's why we're doing the trial.

Greg Guthrie: Thanks, Dr. Braun. Yeah, clinical trials are a safe way to grow our knowledge in cancer care and treatment. And definitely, as Dr. Roeland said, if we don't have evidence, the evidence in this current guideline to support recommendations, then the only way we can truly find that is by participating in clinical trials. And so I would just note that if you're interested in participating in a clinical trial, talk to a member of your health care team. And there are a number of online resources, such as ClinicalTrials.gov, where people can look for research. That's how we advance the science. So is there anything else people with cancer should know about using cannabis or cannabinoids during cancer treatment?

Dr. Eric Roeland: One key message I think for our listeners is to recognize that people have varying tolerances to this class of medicines. And what I frequently observe is that an older patient is offered an edible by their well-intentioned children who want their mom or dad to start eating more in the setting of their cancer. Unfortunately, I've experienced taking care of people that have had side effects associated with the use of cannabis or cannabinoids leading to even emergency department visits and hospitalizations.

And although these products are overall very safe and you cannot quote “overdose” on them or stop breathing because you're taking too much cannabis, it can be very uncomfortable to feel very confused and unable to stand or walk. That can be prolonged for many people, especially those who feel especially weak during their cancer therapy.

And our loved ones mean well, but sometimes the advice that they're providing could actually cause harm. And sadly, I've had many children of patients who have felt incredibly awful after their loved one had a side effect from these medicines, which actually delayed their cancer care.

Greg Guthrie: Excellent point, Dr. Roeland, thank you for that. Dr. Braun, any final notes?

Dr. Ilana Braun: Yeah, so following on Dr. Roeland's thoughts, I would also add that it's important to think about safe storage for such products, particularly if there are children or pets in the home. Cannabis products sometimes look like medicine and sometimes look like candy or baked goods. And so it's important to store them out of the reach of minors and pets.

And the last thing I'll emphasize is this: if you are living with cancer and medicating or thinking of medicating with cannabis or cannabinoids, please consider sharing this information with your clinicians so that they can help you strategize about an optimal course.

Dr. Eric Roeland: I would like to take a moment to thank the American Society of Clinical Oncology for recognizing that we need to address this important need for people living with cancer. And rather than ignore something that's happening every day in the clinic, ASCO chose to convene a panel of experts and coalesce the data and try to figure out what best practices are in this space.

And to that, I am very proud to be a member of ASCO who chooses to lean into these difficult topics rather than run away. I would also say this is a keen opportunity for everyone to advocate for more research in this space. Because talented folks like Dr. Braun, who want to do research in this space, need advocates, need participants, and need funding to fund this type of research. So again, kudos to ASCO, the members of the panel, and, of course, our patients.

Dr. Ilana Braun: Thank you, Eric, for saying that. I am so grateful to have been a part of this really cutting-edge process. And I think that clinical guidelines will help to de-stigmatize cannabis care in a meaningful way in the oncology clinic.

Greg Guthrie: This has been great. Thanks, Dr. Braun. Thanks, Dr. Roeland. If I can interject, I think one of my biggest takeaways here is every patient, caregiver, if they are or are considering cannabis or cannabinoids, the biggest question is to ask, why am I choosing this? And then to find a member of their health care team and talk to them about that. And that's how we protect each other's health and we ensure the best results possible for everyone. So I want to thank you both so much for this engaging discussion. Dr. Braun, Dr. Roeland, thanks for joining us today. And our listeners, if you'd like to learn more about this guideline, please visit www.asco.org/guidelines. Thanks so much for joining us today, and be well.

ASCO: Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.

And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

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ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so clinical trials described here may no longer be enrolling patients, and final results are not yet available. 

Before any new cancer treatment can be approved for general use, it must be studied in a clinical trial in order to prove it is safe and effective. In today’s podcast, members of the Cancer.Net Editorial Board discuss 3 clinical trials that are exploring new treatment options across kidney, bladder, and prostate cancer.

This podcast will be led by Dr. Timothy Gilligan, Dr. Tian Zhang, Dr. Petros Grivas, and Dr. Neeraj Agarwal.

Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Institute. He has no relevant relationships to disclose.

Dr. Zhang is an associate professor of medicine at Duke University School of Medicine and is a medical oncologist at Duke Cancer Institute. She has served in a consulting or advisory role for Bristol-Myers Squibb and Merck, and has received research funding from Astellas Pharma.

Dr. Grivas is the clinical director of the Genitourinary Cancers Program at University of Washington Medicine. He is also an associate member of the clinical research division at the Fred Hutchinson Cancer Research Center. He has served in a consulting or advisory role for Bristol-Myers Squibb and Merck.

Dr. Agarwal directs the Genitourinary Oncology Program at the Huntsman Cancer Institute at the University of Utah. He has served in a consulting or advisory role for Bristol-Myers Squibb, Merck, and Astellas Pharma.

View full disclosures for Dr. Gilligan, Dr. Zhang, Dr. Grivas, and Dr. Agarwal at Cancer.Net.

Dr. Gilligan: Hi. I'm Dr. Timothy Gilligan from the Cleveland Clinic Taussig Cancer Institute. I'm joined today by Dr. Tian Zhang from the Duke Cancer Institute, Dr. Petros Grivas from the University of Washington and Fred Hutchinson Cancer Research Center, and Dr. Neeraj Agarwal from the Huntsman Cancer Institute and University of Utah. Today, we're going to discuss 3 ongoing clinical trials in kidney, bladder, and prostate cancer.

As you may know, clinical trials are the main way that doctors are able to find better treatment for diseases like cancer. Patient participation is vital for clinical trials. By participating in the clinical trial, you can directly help researchers develop better treatment, reduce side effects, or even reduce the risk of cancer altogether.

The 3 trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers panel from the Trials in Progress abstracts that were presented at ASCO's 2020 Annual Meeting. Because these are ongoing clinical trials, final results from these studies are not available yet. I'd like to note that none of us have any direct involvement with any of these trials. To view our full disclosures, please view the show notes for this episode on Cancer.Net.

We're going to start with Dr. Zhang discussing the trial CheckMate 914. Why don't we begin with who the study is designed for?

CheckMate 914 is a study in the adjuvant setting, so it's a study after patients have had their primary kidney cancers removed, and everybody needs to have a kidney tumor that's either 7 centimeters or larger or have extension beyond the kidney or any nodal involvement. So after their kidney tumors have been removed, this study really is in that timeframe after nephrectomy or after surgery with complete resection of their tumor.

Dr. Gilligan: What's the current standard of care for these patients if they're not on a trial like this?

Dr. Zhang: We often will compare against that standard which currently in the adjuvant setting we either do observation until disease recurrence or there is 1 oral treatment that's approved called sunitinib. But sunitinib really has some controversial data around it, and so it's not often used. And so currently, many patients are still observed as standard of care in the setting.

Dr. Gilligan: And so if a patient goes on this trial, what can they expect?  

Dr. Zhang: So patients who are enrolled to CheckMate 914 are randomized to either a combination immunotherapy called ipilimumab with nivolumab, which is approved in the metastatic setting for kidney cancer, or they're placed on placebo for these 2 treatments, or there is a third cohort that receives nivolumab alone with a placebo of ipilimumab. And so these patients are receiving either active immunotherapies or a placebo, which would be our current standard of care, sort of observation until disease recurrence.

Dr. Gilligan: So patients will either get the current standard, which is observation, or else they'll have 1 drug or 2 drugs if I'm understanding correctly?

Dr. Zhang: That's right.

Dr. Gilligan: What is the hope of this study? What is the outcome that we're hoping to see?

Dr. Zhang: The primary outcome of this study is disease-free survival, so that means time until disease recurrence for all comers. And we're really trying to prolong time until disease recurrence or time until metastasis for these patients. There are some secondary outcomes that are very important as well, so prolonging overall survival as well as the incidence of adverse events that are seen from these treatments. And then there is an independent radiographic assessment to look for disease-free survival intervals as well.

Dr. Gilligan: And the hope is that these treatments will prevent recurrence or at least delay recurrence then?

Dr. Zhang: That's absolutely correct, yes. And we have had 2 other adjuvant trials with immunotherapies in this space of atezolizumab and pembrolizumab, but those trials have finished accruing. And so this is the main ongoing and accruing trial that's looking at active immunotherapy options in this space.

Dr. Gilligan: What risks should patients be aware of that they might encounter if they go on this treatment?

Dr. Zhang: So with all immunotherapies, we talk a lot about the immune mediated adverse events and just the usual rundown of those. And in my clinic, we talk a lot about the common rashes. In the GI tract, it can cause some inflammation or colitis. Very rarely, it can cause some inflammation in the lungs or liver and then very commonly, endocrine dysfunction. So we watch pituitary, thyroid, adrenal, and pancreas function very carefully. But all of these side effects are well described for the ipilimumab, nivolumab combinations as well as nivolumab on its own in the metastatic setting. So most people should know what to monitor for and what we're looking out for and how to manage these toxicities.

Dr. Gilligan: Right. So these are drugs that have been in wide use for some years now, so we have significant experience managing the side effects is what I'm hearing you say.

Dr. Zhang: That's right.

Dr. Gilligan: Is this trial still open to patients?

Dr. Zhang: Yes. This trial is still accruing. It's a global study about to enroll up to 1,600 patients. So it's a very large global trial that is still active and still accruing patients. So I would encourage people and also oncologists to refer patients for the trial at a center close to them if possible.

Dr. Gilligan: And when might we expect results for a study like this?

Dr. Zhang: These adjuvant studies take a while to finish accruing and then it takes a while to finish seeing the data. So I would hazard a guess that we're still years away from seeing the data from this trial.

Dr. Gilligan: So once again, this is for people who have had surgery to remove a kidney cancer and looking at ways to reduce the risk of subsequent relapse. Well, thank you for summarizing that so coherently and succinctly. Let's move on now, and we're going to talk about the trial KEYNOTE-992 with Dr. Grivas. Dr. Grivas, who is this study designed for?

Dr. Grivas: So this is a clinical trial, a phase III clinical trial that applies to patients who opt to pursue what we call bladder preservation, which is an attempt to keep the bladder intact and still try to treat bladder cancer with concurrent use of chemotherapy and radiation. And this bladder preservation approach applies to a proportion of patients with bladder cancer still in the bladder but not spread. And as I mentioned before, the decision to pursue that strategy depends on particular patient characteristics, how the cancer looks on the CAT scans, and also how it looks under the microscope.

Dr. Gilligan: What is the current standard of care for these patients?

Dr. Grivas: So patients who are characterized as great candidates for this bladder preservation approach, because this does not apply to everybody with bladder cancer, the standard of care right now is patients undergo what we call a transurethral bladder tumor resection, which means that the urologists go through the urethra and they resect or remove or scrape, remove the visible bladder tumor, and then the patients undergo concurrent, meaning at the same time, chemotherapy and radiation.

Dr. Gilligan: How does the study aim to improve or change the standard of care? What would be different as a result of the study if it's successful?

Dr. Grivas: So this particular clinical trial, the KEYNOTE-992, is asking the question whether the addition of immunotherapy with 1 of those immune checkpoint inhibitors that activates the immune system, does this addition add value in the combination of chemotherapy and radiation? So the patients are being randomized by a computer system to either getting chemotherapy-radiation, as is the standard of care that we just discussed, or chemotherapy plus radiation which is standard of care, plus the addition of this drug called pembrolizumab, which is an immunotherapy aiming to activate the immune system.

Dr. Gilligan: And it's given at the same time as the chemotherapy and radiation on the study?

Dr. Grivas: That is correct. It's given at the same time. And then there is also some—what we call continuation of pembrolizumab for some time after the end of chemotherapy and radiation, and pembrolizumab in this study is given every 6 weeks.

Dr. Gilligan: And what makes people think that this might be helpful to add this additional treatment?

Dr. Grivas: The notion is that the addition of immunotherapy to chemotherapy-radiation therapy has the potential to make the chemotherapy, radiation therapy work better. What happens sometimes when you give chemotherapy-radiation, this can actually result in a killing of some cancer cells and the contents of those cancer cells can be released, and they may be recognized by the immune system and stimulate the immune response. So if you combine that chemotherapy and radiation with immunotherapy with this agent that stimulates the immune system, the assumption is that this may work better compared to chemotherapy and radiation alone. But we have to do this trial to confirm whether this is true or not.

Dr. Gilligan: So patients going on the study, basically, either they'll get the standard of care, which is the chemotherapy and radiation, or the standard of care plus the addition of immunotherapy to see if that results in better outcomes. Am I understanding that correctly?

Dr. Grivas: That's exactly right. And the outcomes are being measured by how many patients maintain the bladder intact, in place without the need to remove it, without the need for cystectomy. And also, at the same time, we want to see if those patients can maintain a cancer-free status, so whether the treatment results in a cancer-free state and whether we are measuring a recurrence as Dr. Zhang mentioned before, if the cancer comes back. And also, of course, we measure how many patients are alive over time. So the goal is to see if we can improve upon the rate of patients with no cancer coming back, no recurrence, and being able to keep the bladder intact if possible.

Dr. Gilligan: So for both of these trials, the question seems to be if we intensify treatment, can we increase the cure rate and keep patients cancer-free longer?

Dr. Grivas: That's exactly right, and that's the promise or the assumption of this trial, whether the addition of immunotherapy to chemotherapy and radiation can improve those chances.

Dr. Gilligan: What are the known risks that patients should be aware of?

Dr. Grivas: As Dr. Zhang mentioned before, every time we have the immunotherapy in clinical trials or in clinical practice, we have to do a good job educating, of course, all the medical providers, team members, and the patients for early recognition and reporting of what we call immunotherapy-related potential side effects. And as we discussed earlier, any organ of the immune system could be a target of an activated immune system. The reality is that if the side effects from immunotherapy happens, usually it's a mild to moderate degree and usually can be managed by holding of the immunotherapy drug and maybe sometimes give some steroids to cool down the immune system. Obviously, we need to be extra vigilant, and I always err on the caution of overeducated patients to avoid underreporting so we make sure we know ahead of time if a side effect happens.

Dr. Gilligan: Is there any reason to be worried that immunotherapy could make the side effects of chemotherapy and radiation worse?

Dr. Grivas: It's a great question, and we have to look in that during the course of the trial. The notion is so far, based on the available data, that it's safe to combine chemotherapy, radiation, and immunotherapy. There have been some early data suggesting that, and this is reassuring. At the same time, we need, again, to be extra vigilant, again, over-educating our patients to report any changes so we can be able to compare the potential side effects in the 2 groups. But so far, it seems to be a feasible strategy.

Dr. Gilligan: Good. And is this trial still open for patients?

Dr. Grivas: Yes, it is open and accruing patients actively, and I think it's a great opportunity for patients to discuss with their providers, urological oncologists, medical oncologists, radiation oncologists, whether they could be good candidates for this bladder preservation approach, if that's a good fit for them and the particular cancer at hand, and if so, whether they can be candidates for this trial or another trial called SWOG 1806, which is in the same space and setting.

Dr. Gilligan: And when might we expect results from the study?

Dr. Grivas: It may take time because this trial is still early in the accrual process. It may take a few years. The current estimate is probably 2026, so 5 years from now. However, the faster these trials accrue, maybe the faster is to have the results. So this might have been overestimation, but it depends with how quickly the study will accrue patients. It's a very exciting study and definitely, I encourage patients to discuss this and the SWOG 1806 with their providers.

Dr. Gilligan: Thank you very much. We're going to move on now, and Dr. Agarwal will tell us about the KEYNOTE-991 study. Dr. Agarwal, who is this study designed for?

Dr. Agarwal: This is a study which is designed for patients with newly diagnosed metastatic castration-sensitive prostate cancer. In simple words, this is for those patients who have been diagnosed to have a prostate cancer which has gone to different parts of the body.

Dr. Gilligan: And what's the current standard of care for these patients if they don't go on the study?

Dr. Agarwal: Fortunately, the current standard of care has gone through a paradigm shift in the last 5 to 6 years. It started with chemotherapy with docetaxel being approved for these patients in 2014 with 2 positive clinical trials showing benefit for docetaxel chemotherapy as far as improvement of survival is concerned. After that, 3 more drugs known as novel androgen axis inhibitors, so deeper blockade of androgen pathway, which is a driver behind prostate cancer progression. So these 3 drugs, abiraterone, or also known as Zytiga, enzalutamide, also known as Xtandi, and apalutamide, also known as Erleada. These 3 drugs and chemotherapy are currently approved agents for our patients with newly diagnosed metastatic prostate cancer.

Dr. Gilligan: And what is this study looking at to potentially change that or to add another option?

Dr. Agarwal: So this study is using the backbone of androgen deprivation therapy, which is standard testosterone suppression therapy, plus enzalutamide or Xtandi. And then patients who are receiving the standard of care therapy with standard testosterone suppression therapy, plus enzalutamide, they will be randomized to pembrolizumab versus placebo. Pembrolizumab is an approved immunotherapy for multiple cancer types and pembrolizumab, also known as Keytruda, works by activating our immune system to fight against cancer cells. In a way, this study is actually testing whether addition of this novel immunotherapy pembrolizumab to existing regimen of androgen deprivation therapy plus enzalutamide is going to improve survival outcomes.

Dr. Gilligan: What do we know about immunotherapy and prostate cancer?

Dr. Agarwal: So far, immunotherapy, as we call them, immune checkpoint inhibitors, many of them are approved for multiple cancer types. They have not been successful as single agents in the context of advanced prostate cancer. So this is a trial which is testing whether immunotherapy, the pembrolizumab is going to be effective in combination with enzalutamide and testosterone suppression therapy.

Dr. Gilligan: So patients will get the standard of care therapy either way. And then the question is, does adding immunotherapy make it even more effective than it is without it? Is that correct?

Dr. Agarwal: That's true. The primary end points of the trial are overall survival and radiographic progression-free survival, which basically means the investigators are going to look for improved survival, overall survival, and delaying of disease progression by adding pembrolizumab.

Dr. Gilligan: And we've already discussed the risks of immunotherapy on the previous 2 trials, but can you tell us again for patients who are particularly interested in this study what risks should they be aware of?

Dr. Agarwal: So pembrolizumab belongs to a class of drugs known as PD-1 or programmed death 1 receptor inhibitor. Usually, this class of drug, as a class, these are highly well-tolerated drugs and only a small number of patients, I would say less than 5% of patients, would develop grade 3 or 4 side effects which will require treatment with corticosteroids like prednisone. And those side effects usually happen when these immune checkpoint inhibitors are able to activate the immune system beyond desired limits. And when the immune system is activated to very high levels, the immune system can attack our own body and can result in diarrhea, skin rashes, liver enzyme abnormalities, and if not controlled in time can lead to hepatitis, which is inflammation of the liver, inflammation of the lungs causing pneumonitis or cough, dry cough mostly. So these are the common grade 3, 4 side effects which happen in up to 5% of patients with pembrolizumab.  

Dr. Gilligan: Just for our listeners in case they're not familiar, when you talk about grades 3 and 4 toxicities, what should they understand that to mean?

Dr. Agarwal: In simple words, I would say grade 1 and 2 side effects are the ones which do not require any systemic therapy with steroids. Patients can go on with their daily activities without much problems. And mostly, these are controlled with medications which are over-the-counter. Even if we use prescription medicines, they're usually not able to affect the patient's overall lifestyle or quality of life. So these are the side effects which are pretty easily manageable mostly with over-the-counter drugs, symptomatic drugs, and patients lifestyle and quality of life are usually not affected by the side effects. And grade 3 and 4 side effects are those which require intensive therapy, in this context, with prednisone or corticosteroids sometimes requiring hospitalization and requiring multidisciplinary care with other specialists who are specializing in gastroenterology or pulmonology or on many other specialties. So that's how I would like to simplify the definition of grade 1, 2 versus grade 3, 4 side effects.

Dr. Gilligan: That's great. Thank you very much. Is the trial still open for accrual? Can patients still go on it?

Dr. Agarwal: Yes. Yes. Trial actually just opened for accrual, which is good news for our patients. And I would like to highlight that patients who have been diagnosed with newly diagnosed metastatic prostate cancer and they have started hormonal therapy like androgen suppression therapy, they still have 3 months to enroll in the trial. So if you have been diagnosed with metastatic prostate cancer and if you have started the treatment with testosterone blockade therapy, you can still go on the trial. You have 3 months to go on this clinical trial. And if you have started chemotherapy with docetaxel, which is a standard of care for our patients with this diagnosis, you can still go on the trial after receiving up to 6 cycles of chemotherapy with docetaxel. So this trial allows actually patients to go on the trial for up to 3 to 6 months after being diagnosed with metastatic prostate cancer.

Dr. Gilligan: So that's very helpful to know. At the conclusion of chemotherapy, they would then start the enzalutamide and either the pembrolizumab or placebo?

Dr. Agarwal: That's correct.

Dr. Gilligan: Well, great. And when do we expect to see results from the study?

Dr. Agarwal: So as we know this, which is great news for our patients, survival has gone up by almost 2 to 3 fourths over the last 10, 15 years, and in this disease setting, any trial takes up to 5 to 6 years to show results. So I estimate based on the available information on the ClinicalTrials.Gov website, the trial is scheduled to finish in 2026.

Dr. Gilligan: I see. Well, great. So thank you very much. Thank you all 3. That's hopefully a helpful summary of these 3 important new trials.

Dr. Agarwal: Yes, it's a pleasure to be here, Tim.

Dr. Grivas: Thank you so much.

Dr. Gilligan: Thank you. Thank you for listening to this podcast. There are many different clinical trials currently enrolling people with genitourinary cancers. If you're wondering whether participating in a clinical trial might be right for you, please talk to your health care team.

ASCO: Thank you, Drs. Gilligan, Zhang, Grivas, and Agarwal.

Visit www.cancer.net/clinicaltrials to learn more about participating in clinical trials. All treatments have side effects—please talk to your health care team about possible side effects to watch out for.

And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests’ statements on this podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses.

The theme of the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting was “Partnering With Patients: The Cornerstone of Cancer Care and Research.” From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need.

In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting, and explain what it means for people with cancer. In today’s episode, our guests will discuss new research in breast cancer, lymphoma, multiple myeloma, and brain tumors.

First, Dr. Norah Lynn Henry discusses new research in early stage and metastatic breast cancer. Dr. Henry is Professor and Interim Chief of the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the 2023 Cancer.Net Associate Editor for Breast Cancer.

You can view Dr. Henry’s disclosures at Cancer.Net.

Dr. Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of the most exciting new research in breast cancer that was presented at the 2023 ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. First, I'm going to give a very brief overview of the types of breast cancer, then talk about some research that was presented on both early-stage and metastatic breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We treat those cancers with anti-estrogen or anti-endocrine treatments, which block estrogen or lower estrogen levels. Other breast cancers are called HER2-positive. These are often more aggressive cancers. But because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or HER2. These are called triple-negative breast cancer and are also often aggressive cancers. Most of the results I'm going to highlight today are treatments for estrogen receptor-positive and HER2-negative breast cancer. One of the main stories from the ASCO Annual Meeting was the result of the NATALEE trial. At the present time, for patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who were at high risk of having their breast cancer come back, the currently recommended treatment is anti-endocrine therapy. Based on the results of a prior trial called monarchE, we also consider adding a medicine called abemaciclib, which turns off some enzymes in the cell that are called CDK4 and CDK6, which are known to make estrogen receptor-positive breast cancer cells grow. Abemaciclib can further reduce the risk of cancer recurrence compared to endocrine therapy alone, but it does have some side effects, most commonly, diarrhea.

In the NATALEE trial, which was presented for the first time at this ASCO meeting, researchers studied a similar type of medication called ribociclib. It acts similarly to abemaciclib, although it is more likely to cause low blood counts and less likely to cause diarrhea. Ribociclib is currently routinely used in combination with anti-endocrine therapy to treat patients with metastatic estrogen receptor-positive breast cancer but is not yet routinely used in the early-stage setting. In the NATALEE trial, patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who are at high risk of breast cancer recurrence were enrolled. Half the patients were treated with just standard anti-endocrine therapy and half also received ribociclib for 3 years. After the 3-year treatment period, those who received both ribociclib and anti-endocrine therapy were about 25% less likely to have their cancer come back compared to those who received only anti-endocrine therapy. Overall, the medication was quite well tolerated. It is important to note that this drug is not yet FDA-approved in the setting.

The remaining trials I will highlight are for treatment of metastatic breast cancer. There were many trials examining how best to use drugs that we are actually already using in the clinic. For example, many presentations were about the CDK4/6 inhibitors that I just mentioned. Typically, patients who have just been diagnosed with estrogen receptor-positive, HER2-negative metastatic breast cancer get treated with anti-endocrine therapy plus a CDK4/6 inhibitor. One trial called SONIA examined whether this is the right approach, or whether patients should just get the anti-endocrine therapy up front and hold off on starting the CDK4/6 inhibitor medication until a later time.

It appears that this delayed approach would reduce symptoms as well as cost of the medication, while not reducing benefit from the treatment. Therefore, it appears it is likely fine for some patients to get just anti-endocrine therapy alone initially. However, we don't know how to identify those patients. Researchers are still figuring out which patients should follow this new treatment plan and which should keep getting the double therapy at the beginning. Some more to come in the future. There was a different trial called PADA-1 that included patients taking anti-endocrine therapy and the CDK4/6 inhibitor, palbociclib, upfront. Those patients were monitored using a blood test, looking for a mutation or a change in the estrogen receptor in the cancer. Patients who had that mutation either remained on the same treatment that they'd been on or switched to the next line of therapy, even though their scans didn't show any progression of their cancer. Overall, this switching strategy looks like a very promising approach for managing patients since it may help patients' cancer respond to treatment for a longer period of time. Although this approach is not yet officially recommended according to our guidelines. In another example, many patients with all types of metastatic breast cancer are treated with a drug called capecitabine, also known as Xeloda. Although this drug is effective for many cancers, many patients experience hand-foot syndrome, nausea, diarrhea, and mouth sores. In the X7-7 clinical trial, the researchers compared the official standard FDA-approved dose based on a patient's height and weight and given for 14 days followed by 7 days off. That was compared to a fixed dose of treatment given 7 days on and 7 days off. The trial found that the fixed-dose regimen was easier to tolerate, but importantly, the benefit from the 2 doses and schedules of treatment appears to be similar.

Therefore, we will likely be using this lower dose, 7 days on and 7 days off, for most of our patients who receive treatment with capecitabine for metastatic breast cancer, since it is likely to improve their quality of life while not negatively impacting the potential benefit they receive from the therapy.

There were a lot of other research findings presented that are related to treatment for both early-stage and metastatic breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, including a new antibody-drug conjugate against HER2, as well as other new anti-endocrine and targeted treatments. We eagerly await the results of large, randomized trials so the drugs that work can be used to treat patients with breast cancer. But for now, that's it for this quick summary of important research from the 2023 ASCO Annual Meeting. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you.

ASCO: Thank you, Dr. Henry.

Next, Dr. Christopher Flowers discusses new research in lymphomas and multiple myeloma. Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and Division Head ad interim of Cancer Medicine. He is also the 2023 Cancer.Net Associate Editor for Lymphoma.

You can view Dr. Flowers’ disclosures at Cancer.Net.

Dr. Flowers: Hello. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma and interim division head for cancer medicine at the University of Texas MD Anderson. And it's my pleasure to talk to you today in this Cancer.Net podcast about latest updates in the hematological malignancies focused on lymphoid cancers from the American Society of Clinical Oncology Annual Meeting. The ASCO Annual Meeting every year is an exciting time for latest updates in the care of patients with cancer. And in particular this year, there were 3 abstracts that I'd like to highlight that were presentations at this meeting about lymphoid malignancies that have potential significant impact for patients over time. The first 2 come from a special session that was on late-breaking abstracts that were latest advances from clinical trials. The first is from the ZUMA-7 trial. This is a trial looking at axicabtagene ciloleucel, a chimeric antigen receptor T-cell therapy, or CAR T-cell therapy. The CAR T-cell trial in question here was led by Jason Westin, who's a colleague of mine at MD Anderson. And MD Anderson is a partner with Kite pharmaceutical company that is a manufacturer of this and has a research alliance with that group.

In the ZUMA-7 trial, this was a trial that involved the use of CAR T-cell therapy in comparison to standard-of-care therapy, which typically would be aggressive chemoimmunotherapy followed by autologous stem cell transplantation for patients with relapse of large B-cell lymphoma. As many of you may know, large B-cell lymphoma is a kind of lymphoma that is potentially curable with standard frontline therapy. And when patients relapse, the standard of care historically had been for patients to receive autologous stem cell transplantation, which is also potentially a curative therapy. This trial to do a ZUMA-7 trial compared patients who received the typical standard of care, the autologous stem cell transplant following the aggressive chemoimmunotherapy regimen for patients who had relapsed early after their initial therapy, so within 12 months, or were refractory, meaning that they did not respond to their initial therapy. And this was compared to the axicabtagene ciloleucel or axi-cel CAR T-cell therapy. The initial publication of the trial came out in the New England Journal of Medicine in 2022 and showed that the event-free survival for patients who receive CAR T-cell therapy was superior.

This update of the ZUMA-7 trial at the ASCO Annual Meeting that was presented by my colleague, Jason Westin, discussed the overall survival of the study, and in this update, it showed that overall survival was also improved for patients who received axi-cel as opposed to standard-of-care therapy. And now with a median follow-up of a little bit more than 47 months, axi-cel demonstrated superiority that was statistically significant and clinically meaningful over the traditional standard of care.

In that same session, there was another trial looking at CAR T-cell therapy for patients with multiple myeloma. This was a BCMA-targeted CAR T-cell therapy that was presented by Dr. Dhakal in that session providing results from the CARTITUDE-4 global randomized phase 3 clinical trial. That was a trial that involved 419 patients where patients were randomized to cilta-cel CAR T-cell therapy for myeloma or standard-of-care therapy, which in this case included combination therapy. And in this trial, this showed that single agent with a single cell-to-cell infusion significantly improved progression-free survival versus standard of care for patients with multiple myeloma who had 1 to 3 prior lines of therapy and were refractory to lenalidomide. This is also a meaningful advance for patients with this disease.

And the final abstract that I'll mention is an abstract that was presented by Dr. Alex Herrera from City of Hope and was presented in the Plenary session. And it was really exciting to see a Plenary session presentation focusing on lymphomas. So this trial presented by Dr. Herrera was led by the Southwest Oncology Group. Dr. Sara Ahmed from MD Anderson, from my institution, was a participant and actively engaged in this clinical trial. This trial was a success in a number of ways. First, it involved both pediatric and adult patients and is one of the first trials of its kind to involve both large populations of patients with pediatric lymphomas as well as adults with lymphomas. It helps to consolidate the approaches that we use for Hodgkin lymphoma, both in the pediatric population and the adult population. It also represents a major advance in the ways that we conduct clinical trials in the United States in that this clinical trial finished ahead of schedule in terms of completion of the trial with collaboration from the adult and pediatric groups across the National Clinical Trials Network. As I mentioned, this was presented by Dr. Alex Herrera in the Plenary session and involved patients with stage 3, 4 Hodgkin lymphoma, where patients were randomized 1 to 1 either to receive an anti-PD-1 therapy, nivolumab, with chemotherapy, the AVD chemotherapy regimen, or the antibody-drug conjugate, brentuximab vendotin, combined with that same AVD chemotherapy. And what this showed in 994 patients who were enrolled from 2019 to 2022 was that there was a benefit for patients who received the combination of nivolumab AVD or NAVD versus the group that received brentuximab and AVD. It improved the progression-free survival in patients with advanced-stage Hodgkin lymphoma.

In this trial, few immune-related adverse events were observed and a lesser number of patients went on to receive radiation therapy, which is also a benefit for patients with Hodgkin lymphoma. And this concludes my presentation of abstracts at the ASCO Annual Meeting and really exciting advances for patients with lymphoma that were presented this year.

ASCO: Thank you, Dr. Flowers.

Finally, Dr. Roy Strowd discusses new research in treating brain tumors, including those in people with von Hippel Lindau syndrome. Dr. Strowd is a neurologist and neuro-oncologist at Atrium Health Wake Forest Baptist Comprehensive Cancer Center. He is also the 2023 Cancer.Net Associate Editor for Central Nervous System Tumors.

You can view Dr. Strowd’s disclosures at Cancer.Net.

Dr. Strowd: Hello, everyone. This is Roy Strowd. I'm a physician neuro-oncologist at Wake Forest University School of Medicine in our comprehensive cancer center. And I’m really excited to be with you for this podcast on important CNS or brain tumor updates from the 2023 ASCO Annual Meeting. I don't have any relevant disclosures for the research that we'll discuss today. It was a really exciting meeting. It was actually a really fun meeting to be a brain tumor doctor at ASCO this year. So I'm really excited to talk with you about some important updates. And I think it's actually a really important time to be a patient and a caregiver and know some of the things going on in brain tumor care. So I'm going to dive into 3 studies. And one that we just have to talk about, and this was a really exciting study called the INDIGO study. At ASCO, if you present a study, you want to have a Plenary presentation, you want to be up on the big stage presenting your work. And brain tumor studies aren't always on the big stage. We just haven't had enough really good treatments out there for brain tumor patients over the years. And this year, we had a Plenary presentation, a really big study, making a big splash. And that was this INDIGO study. So I'm going to spend a few minutes talking about that study. I want brain tumor patients and caregivers to know about this and know about some of the important updates from the Annual Meeting.

The study was called the INDIGO study, and it's a phase 3 study. So when you think about clinical trials, there's a phase 1, phase 2, phase 3. That phase 3 is that last step, that last hurdle that a drug needs to overcome to move towards approval. And a positive phase 3 study is really exciting for the field and means that we may have a new treatment that will change how we take care of brain tumor patients. And that's what this study was. It was also a really unique study. So it's looking at a different group of brain tumor patients, patients that have an IDH mutant glioma. Most common brain tumors that we see are the glioblastomas. And those are often and really, by rule, IDH wild-type. IDH is a gene. It's called the isocitrate dehydrogenase gene. And it's one of these really important genes for us to understand how brain tumors are going to work and how they act and it turns out, with this study, how they may respond to treatment.

So this study looked at enrolling patients that had an IDH-mutant low-grade glioma, or a grade 2 glioma. Those are those often slower-growing, but they continuously grow tumors that occur early in life, typically in the 30s or 40s for young people. And we haven't really had a lot of good treatments for these patients. And so this study looked at giving a new drug that's called vorasidenib. It's hard to say vorasidenib. And it's an IDH mutant inhibitor. So it attacks that IDH mutant gene that makes these tumors what they are. And it's been undergoing development for many years. It's an exciting treatment because it's what we call a molecularly targeted treatment. It specifically targets that IDH gene that makes the low-grade tumors low-grade tumors. This study enrolled 331 patients, so a large group of patients. Half of those patients received the drug, the vorasidenib, and half received placebo. And that's pretty uncommon in cancer. We don't often do studies that are placebo-controlled studies. But for these patients, there's often not a good treatment early in the course, they get surgery. And for patients that don't need an additional treatment, we do surgery and then we wait and watch and see what happens. And that gives us an opportunity as a brain tumor community to figure out whether this type of treatment will help prevent the need for a next treatment, prevent the need for radiation and chemotherapy. And so that's what was looked at in this study. And there was some really exciting data.

So I'm going to go through a few numbers, but we just got to talk about these numbers because they're really important. So at 14 months, 28% of the patients receiving the drug vorasidenib had progressions. That's about a quarter of patients compared to half that received placebo. So that's a big improvement in the number of patients whose tumor grew. So this drug prevented tumor growth in these patients. And that's exactly what we want. That's why we develop drugs, is to prevent tumor growth. When we look at the time that those patients had until they needed a next treatment or until their tumor grew, it was over 2 years of time patients receiving the drug when their tumor grew versus less than a year, 11 months for those receiving placebo. So it's adding a lot of time for brain tumor patients without tumor growth or without needing another treatment. And typically, these patients with low-grade gliomas would need something like radiation therapy or chemotherapy. And those are good treatments, and we need those treatments. But they can have toxicity. And so this is the type of drug that could prevent that toxicity, cognitive decline, other problems that can happen with chemotherapy that those patients didn't potentially suffer.

So there are some important things that we learned from the INDIGO study that I would want you to take away, kind of what do these data mean? The first is that we can target this IDH gene. And that's really important for our field. And it means if you're a brain tumor patient, knowing whether your tumor is IDH mutant or IDH wild-type is important, and that's something I want brain tumor patients to ask me as a neuro-oncologist and ask their cancer doctor because that's important in deciding treatment for them. The second is this medicine vorasidenib, it gets into the brain. And that's one of the big challenges that we have in brain tumor care in developing drugs is we need things that get into the brain. And this study really shows that this is a good medicine. There's a number of IDH inhibitors, but this medicine vorasidenib is one that we want to specifically think about for our patients. And this is a practice-changing study. So for the first time, we now have a treatment that works for grade 2 gliomas and really prevents the need for radiation therapy and chemotherapy. So those are 3 important things to take away from this.

There's a number of things that we don't yet know. This medicine is not available. So patients coming in and emailing me and calling me, we don't have it yet. And after a big phase 3 study like this, this is announced. There's still a number of steps that need to happen to make sure that this can be delivered to patients safely and we can get it out there. And that's in partnership with groups like the FDA, the Food and Drug Administration, and others. So this is an important conversation to have with patients, neuro-oncologists, and to know that this is something that's on the horizon. Two other things is we don't know if this is going to work for all brain tumors. In particular, for these IDH wild-type glioblastomas, the most common brain tumor, this probably is not a good therapy that we don't have any data to suggest that it would work. They don't have that IDH mutation. And so this is important for some brain tumor patients but not for everybody. And that needs to prompt a conversation with the cancer doctor. And it may not work at all times. So there's some data to suggest that this is really a drug that's best given early in the course of treatment and not later on. And so it is something that I want my patients to be aware of at the first time that I see them so we can be deciding what kind of the right time is.

So I want to give folks 2 take-homes from this study and summarize a few of these things that we heard about because it's such an important study. So what are the 2 take-homes from the INDIGO Study? The first that I wrote down is targeting IDH mutation in glioma works. And that's a groundbreaking discovery from this. This is really important for our field. IDH mutations have been important to diagnose brain tumors but have never been really a therapeutic target. And this changes the landscape, and we can now target IDH mutations in gliomas. And that's really important. The second thing, the second real take-home message, is we can safely delay radiation therapy and chemotherapy in some patients with these lower-grade gliomas, potentially with IDH mutation and IDH inhibition. And that's really important. Chemotherapy and radiation therapy are important, but if we can delay those treatments and prevent side effects, that could be helpful for some of our patients. So really important update from ASCO and what I want to spend most of the time on our podcast focusing on this INDIGO study. But there were a bunch of other things going on in brain tumors at ASCO, as there always are. And I want to highlight 2 studies about some things that the groups of patients may be interested in knowing that happened at the meeting.

The first is a study called the INB-200 study. And this is a phase 1 study, so it's earlier in development. But it's an immunotherapy study. And brain tumor patients and caregivers will know that we've really wanted to find an immunotherapy that works for brain tumors. And we haven't yet. And we're still not there, but this study is an important step in that direction. So this study from a group at the University of Alabama looked at something called gamma delta T cells. And T cells are really important. They're part of the anti-tumor response. They're what the body uses to attack the tumor. So we like those T cells. And particularly, these gamma delta T cells are important in targeting tumor cells in glioblastoma cells. They're also unique. They can avoid the toxicity of chemotherapy. Radiation therapy and chemotherapy suppresses the T cells. They make some go down, or decreased in number, which is not what we want. And these gamma delta T cells were genetically created so that they were resistant to chemotherapy. And that's really, really important. We want an immunotherapy that works and one that isn't suppressed by our other treatments. And that's been a real barrier for glioma patients.

So in this phase 1 study, they found the right dose of these gamma delta T cells, and that's the goal of a phase 1 study. But there were some early signs that this may be changing the tumor. One of the patients underwent surgery before and after they got this infusion. And we were able to see this. Investigators were able to see the gamma delta T cells up in the tumor. So this doesn't change practice. Patients don't need to go out and seek out the gamma delta T cells yet. But it's one of those early findings that says that we need to keep looking at immunotherapy. And as a community, this is something we need to keep focusing on.

And then the last abstract and study I wanted to focus on is for a rare disease. This would not be something that would be relevant for all of our listeners and the brain tumor patients but for a subgroup of patients that have a condition called VHL, or von Hippel-Lindau. And von Hippel-Lindau is a genetic condition. So, most brain tumors are not inherited. You don't get it from a mom or a dad or pass it on, except for these patients, you do. And it comes from a gene that's inherited in families called the VHL or the von Hippel-Lindau gene. And these patients are predisposed to get tumors all throughout the body and the kidneys and the brain and the eye. And this is a lifelong disease where these tumors can really grow slowly over time and cause significant problems. And in the past few years, there's been a new treatment called belzutifan. Belzutifan is the name of this drug that has been shown to be effective in the kidney tumors for patients with VHL. And at ASCO this year, there was a new study showing that it's also effective in treating the brain tumors for these patients. And that's really important. We just haven't had a treatment other than surgery or radiation therapy for these tumors. And oftentimes, they grow after surgery and radiation therapy and we need an additional treatment.

So in this study, the investigators looked at, "Does this drug belzutifan work for treating the CNS tumors, hemangioblastoma?" And found that around 50% of patients had a response, so a shrinkage in the size of the tumor. 90% of patients had control of their brain tumor disease, which is really important. And it worked really quickly, so it worked in about 3 to 5 months, which is shorter than what we would see for the kidney tumors. So that's exciting news for VHL patients, patients with von Hippel-Lindau, and another important update from the 2023 ASCO.

So thanks for listening to this update of CNS brain tumors at the 2023 ASCO Annual Meeting. Again, I'm Roy Strowd, a neuro-oncologist at Wake Forest University School of Medicine. Delighted to bring you this brief summary of new research in the field.

ASCO: Thank you, Dr. Strowd.

You can find more research from recent scientific meetings at www.cancer.net.

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