Podcasts about sumanta monty pal

Play Episode Listen Later Nov 10, 2022 28:34

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 Editorial Board members discuss new research in gastrointestinal and genitourinary cancers presented at this year's ESMO Congress, held September 9-13 in Paris, France. First, Dr. David Ilson discusses treatment advances in liver, colorectal, and gastric, or stomach, cancers. Dr. Ilson is an attending physician and member at Memorial Sloan Kettering Cancer Center and a professor of medicine at Weill Cornell Medical College. You can view Dr. Ilson's disclosures at Cancer.Net. Dr. Ilson: Hi, I'm Dr. David Ilson from Memorial Sloan Kettering Cancer Center in New York. I'm a GI medical oncologist, and it's my pleasure today to review some important presentations in GI cancers from the recent ESMO meeting in Paris from 2022. I have no relevant relationships to disclose for this discussion. So, important presentations were made in hepatocellular cancer, in colorectal cancer, and gastric and other cancers, and I'm going to highlight some of the key presentations from the meeting. One of the most anxiously awaited presentations was one in hepatocellular or liver cancer. For patients that have advanced disease who are not candidates for surgery or local treatments, standard therapy now, it used to be lenvatinib and sorafenib, and that's now been replaced by the combination of an immunotherapy drug, atezolizumab combined with the drug bevacizumab. That's the new standard of care. And recently, we had a promising data for another immunotherapy combination using the drug durvalumab combined with tremelimumab. So what we saw this year was another important global study looking at the first-line use of immunotherapy in hepatocellular cancer. This trial took 794 patients with advanced hepatocellular cancer and assigned them to a standard treatment with a drug called lenvatinib. Lenvatinib and sorafenib were the old standard treatments for hepatocellular cancer. And lenvatinib alone was compared to a combination of lenvatinib and pembrolizumab, an immunotherapy drug. The primary endpoint was to see whether adding immunotherapy to lenvatinib improved survival. And this was a negative trial. It did not show an improvement in survival for adding pembrolizumab to lenvatinib over lenvatinib alone, and there was really no significant difference in the time that patients were on treatment. The response was slightly higher with the addition of pembrolizumab to lenvatinib, but again there was no survival difference. So this combination will not move forward. And again, as I said earlier, the new standard first-line treatment is atezolizumab plus bevacizumab. In colorectal cancer, probably one of the most exciting presentations was the use of immunotherapy treatments in locally advanced colon cancer. There is an important subset of colorectal cancer that has what's called an MSI-high status. MSI-high colon cancers are very responsive to immunotherapy drugs, and there has been a lot of interest in patients with localized colorectal cancer using immunotherapy drugs prior to surgery rather than conventional chemotherapy or radiation. So this important trial looked at 112 patients with localized colorectal cancer. Most of the patients were stage 3, and they all were documented to have this MSI-high status, which indicated a higher chance of response to immunotherapy. And patients received a brief course of immunotherapy, 2 doses of the drug nivolumab combined with 1 dose of ipilimumab over only 6 weeks followed by surgery. What they showed in these 112 patients who went to surgery, there was almost 100% response to this treatment. In fact, almost two-thirds of patients had no cancer found at surgery, even only after several weeks of immunotherapy. And in the 112 patients treated, there have been no recurrences in any of these patients. So it's quite remarkable that immunotherapy could induce a complete remission in two-thirds of patients, and that was only after a few weeks of exposure of the drug. So I think we're going to see more interest in using immunotherapy treatments as a potential pre-surgical treatment for colon cancer. And we could argue with such a high rate of complete remission, if we gave immunotherapy longer, maybe we could consider nonsurgical management, to just keep treating the patients with immunotherapy. This is actually the case that's now been seen in rectal cancer, a recent study presented from my institution where they treated patients with rectal cancer with immunotherapy, and we also achieved 100% remission, and none of the patients in this small study required surgery. So I think this important study, which is called the NICHE-2 trial, indicates a high degree of effectiveness of immunotherapy in MSI-high colon cancers. And certainly, it raises interest in using this as a preoperative treatment and potentially could lead to some patients getting treatment with immunotherapy alone without surgery. Then I'm going to comment a little bit about advanced metastatic colon cancer. Another important presentation was studying a new drug called fruquintinib. Fruquintinib is an oral drug that targets the VEGF pathway, which is an angiogenesis pathway in colon cancer. Standard treatment for colon cancer when it's stage 4 disease is now use of chemotherapy, like FOLFOX and FOLFIRI, drugs like bevacizumab, cetuximab, and panitumumab. And in more chemotherapy-resistant cancers, we use drugs like regorafenib and TAS-102. So this trial looked at a large group of patients, over 690 patients who had received all conventional treatments. They had progressive disease on all conventional treatments, including the late-line drugs regorafenib and TAS-102. And this was a placebo-controlled trial in which patients either received the drug fruquintinib or they received placebo plus supportive care. It was reasonable to offer a placebo in this trial because there really was no other standard treatment option for these patients. The primary endpoint of overall survival was improved with fruquintinib. Survival was improved with a reduction in the risk of death by about 30% and improvement in time on treatment. Very few patients responded to fruquintinib, so this was largely a drug that stabilized the cancer, but it did lead to modest improvements in time on treatment and modest improvements in survival. So this drug may potentially be evaluated as a new treatment option in very chemotherapy-resistant colorectal cancer. I just want to mention briefly another new class of agents for which we had data presented at the ESMO meeting. These are drugs that inhibit a mutation in their cancer called KRAS G12C. There are promising drugs that target this pathway. And there were 2 drugs that were followed up on at ESMO, one was a drug called sotorasib and another drug was adagrasib. These are drugs that target KRAS G12C mutations in colon cancer. And both of the trials that were presented used these drugs combined with drugs that target the EGFR pathways, so either panitumumab or cetuximab, and very encouraging responses were seen on these trials. The trial that looked at the combination of adagrasib plus cetuximab achieved a response in about 46% of patients, which is very encouraging. The trial that studied sotorasib, combined sotorasib with panitumumab, and they observed a 30% response, and some of these responses were durable. So the take-home message is that these drugs, adagrasib and sotorasib, are promising new agents to target KRAS G12C mutations in patients with advanced colon cancer and indicate that we may get even a higher degree of activity when we add EGFR-targeted drugs including panitumumab or cetuximab to these agents. So the other area that I want to comment on is gastric cancer. Recently, in the United States, we had a regulatory approval for the drug trastuzumab deruxtecan in patients who have HER2-positive gastric cancer that's advanced and is being treated with chemotherapy alone, HER-2-positive patients who had received previous trastuzumab or Herceptin. So trastuzumab deruxtecan is a promising drug used in patients that develop resistance to trastuzumab. So there was an update of the trial called Gastric-DESTINY02, which was a phase 2 trial of trastuzumab deruxtecan in Wwestern patients as a second-line treatment for patients with HER2-positive gastric cancer, and the updated analysis again showed a promising response in 40% of patients. The response duration was about 8 months, and patients achieved a survival of a year or more. So this updated presentation really reinforced that this is an active drug for patients with HER2-positive gastric cancer whose disease progresses on previous treatment with trastuzumab. So this was a very exciting ESMO meeting. There were a lot of other studies and important presentations, but I've tried to highlight today what I think are the most important as we move forward in trying to identify new treatments for patients. ASCO: Thank you, Dr. Ilson. Next, Dr. Sumanta (Monty) Pal and Dr. Tian Zhang discuss new research in kidney, bladder, and prostate cancers. Dr. Pal is the 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. Dr. Zhang is an Associate Professor of Internal Medicine at UT Southwestern Medical Center and is a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center. You can view disclosures for Dr. Pal and Dr. Zhang at Cancer.Net. Dr. Pal: Welcome to this Cancer.Net podcast. My name is Monty Pal. I'm a medical oncologist in the City of Hope in Los Angeles. I'm thrilled to be here today with my dear friend and colleague, Dr. Tian Zhang from UT Southwestern. Tian, mind giving us a quick intro? Dr. Zhang: Hi, Monty. Great to be here with you today. Tian Zhang at UT Southwestern in Dallas, Texas, where I'm a GU medical oncologist. I'm really excited to talk through the ESMO trials with you today. Dr. Pal: A little bit of housekeeping first. Let's go ahead and get some of our disclosures out of the way. I get travel support from CRISPR Therapeutics and from Ipsen. Tian, how about you? Dr. Zhang: Sure. I've received honoraria from Exelixis, BMS, Genentech, AstraZeneca, and Janssen, all relevant to our discussion today. Dr. Pal: Very good, very good. Well, thank you so much for joining us today. We've got a lot to talk about in about 15 minutes. The first thing that I wanted to chat about is adjuvant therapy. First of all, before we dive into the weeds here, can you just kind of tell our audience what adjuvant therapy is in broad strokes? Dr. Zhang: In kidney cancer, we think a lot about how we might prevent disease recurrence after surgery. So adjuvant treatment refers to systemic treatment that's given after a big surgery. And so in kidney cancer, that's usually after nephrectomy or removal of the kidney. Dr. Pal: Excellent, excellent. You beat me to the punchline. We are going to focus on kidney cancer, no doubt. This year at the European Society of Medical Oncology, or ESMO, meeting, which was held in early September, we actually had some really key studies presented in this space, one of which I'll disclose that I led. Studies I would say were maybe a little bit disheartening there, but nonetheless, I do think we can learn a lot from them. One of these trials was called PROSPER. This was a really interesting study that actually didn't just look at adjuvant therapy but actually looked at treatment before surgery, which we called neoadjuvant therapy. Tian, can you kind of walk us through the design of that trial really quickly? Dr. Zhang: This was a trial done in the ECOG Cooperative Group, and patients were randomized to receiving either nivolumab, which is an immune checkpoint inhibitor, before surgery, followed by a year of nivolumab after surgery, or to surgery and observation with ongoing scans. So it was really trying to look at a perioperative approach of using nivolumab. Dr. Pal: So how about this? Maybe we'll kind of discuss some of these results in amalgam, but maybe let's go through these trial designs first. The second trial that was highlighted this year at ESMO was called IMmotion010. That's one thing that I just love about these studies. They all have very clever names. I don't know what an IMmotion is, but tell us about IMmotion010 and what that trial design looked like. Dr. Zhang: Sure. So IMmotion010, again, also was an adjuvant trial for resected intermediate- and high-risk kidney cancers, randomized folks to either atezolizumab for a year or placebo for a year. And so this is in the context of having had resected kidney cancers and following folks for the treatment results, and the primary endpoint there was disease-free survival. Dr. Pal: Okay. So we've got an immune therapy called nivolumab and the PROSPER trial that was looked at before and after surgery. We've got atezolizumab, a different checkpoint inhibitor that was looked at following surgery. Tell us about the third trial. This is the last study in the space called CheckMate 914. What did that trial look at? Dr. Zhang: That one, again, also a phase 3 adjuvant trial, enrolling folks after surgery that had high-risk kidney cancer and randomized to either the combination of nivolumab with ipilimumab, both checkpoint inhibitors versus placebo. And again, this treated patients for about 6 months and also primary endpoint of disease-free survival. Dr. Pal: Now, whenever we do these studies, we always define them as being positive or negative, and that's really not meant to sort of cast any aspersions on how well the study was done or any really sentiments around the trial itself. It's really objective, and it's based on whether or not a study hits what we define ahead of the trial as being called a primary endpoint. So we actually, in these studies, looked at a primary endpoint of something called recurrence-free survival. And so that's really the proportion of patients who actually are living on without any sort of recurrence of their kidney cancer. I think it might be easy enough to sort of describe whether or not these trials hit that endpoint were positive or negative. What was the final report here on these trials, Tian? Dr. Zhang: Well, Monty, I think all 3 of these trials were, quote-unquote, "negative," and we all had high hopes for all 3 of these trials. And certainly, many, many patients participated, and we will learn eventually a lot from these trials. But none of these 3 met their prespecified primary endpoint of recurrence-free survival endpoint. Dr. Pal: So this is a little bit tricky because we did have these 3 negative studies presented at ESMO this year, but there was 1 positive trial that's adjuvant or postoperative space presented previously and then now published, actually, in the New England Journal of Medicine with an FDA approval to boot. Can you tell us about that, Tian? Dr. Zhang: Well, that one was called KEYNOTE-564 and randomized patients to either a year of pembrolizumab or placebo. And so you're absolutely right. It did show an improvement in disease-free survival comparing pembrolizumab with placebo. And so pembrolizumab is approved in this adjuvant setting after nephrectomy. Dr. Pal: And so this can be kind of a tough space because I can imagine our listeners are hearing this saying, "OK. Well, at ESMO, we've got 3 negative trials looking at postoperative therapy, and we've got 1 positive trial looking at pembrolizumab in the space." So what's one to do in this setting? What are you telling patients these days about whether or not to use adjuvant treatment for kidney cancer? Dr. Zhang: Yeah. I think it's a conversation that patients have with their oncologist after surgery, and it really depends on their own risk factors, their clinical and pathologic features at the time of resection. It depends a lot on patient preferences and their own priorities and things such as their tolerance for toxicity or how often they're coming into the treatment center. And I do think this is a time point where they have a shared decision-making that we can help our patients understand the totality of the data and then decide if a year of pembrolizumab is worthwhile or if they'd rather continue with surveillance after surgery. Dr. Pal: I totally agree with you, and I love that term “shared decision-making,” because it's never one of those situations where I walk into the clinic room and say, "Here's what you're going to do." And it's also never the situation where the patient walks into the clinic room and says, "Here's what I want." It's always this really sort of mutual process, isn't it, where you sort of look at a patient's clinical state. You look at some of the features under the microscope, but then it comes down to really, really lengthy and personal discussions around what that patient wants to get out of treatment. So I think that's very well said, Tian. I'm going to move to actually a different setting, which is termed “metastatic disease.” So we've talked about localized kidney cancer, where the disease is sort of confined to the kidney for the most part. We talked about what we do after we remove visible evidence of disease. But there is, unfortunately, a number of patients where we can't necessarily remove all the disease burden. So we lean more heavily on what we call systemic treatments. These are treatments that enter into the bloodstream either by mouth or through the veins. And in kidney cancer, just to give you a really, really brief synopsis, there's been this huge evolution over time. When I started in the field, it was really the advent of using a single oral therapy for kidney cancer. And over the next five 5 years, we sort of saw this evolution towards using doublet therapies, which is a mix of pills and IVs or maybe IVs alone. And more recently, there's been a lot of excitement. You can probably see where this is going, right? We've looked at 1 drug, and it works. We've looked at 2 drugs, and they seem to work. Logic would perhaps suggest that maybe you could get away with using 3 drugs in concert. So, Tian, this year at ESMO, there was a really important trial called COSMIC-313 that looked at 3 drugs versus 2 drugs. Can you tell us a little bit more about the design of the study? Dr. Zhang: COSMIC-313, the large phase 3 study, which randomized more than 850 patients to either the triplet, as you're speaking of, the cabozantinib, nivolumab, and ipilimumab versus nivolumab and ipilimumab with placebo standing in for cabozantinib. And so this was a very large trial, looking particularly at progression-free survival, comparing the triplet versus the immunotherapy doublet. Dr. Pal: And then tell us about the results of this because I have to tell you. I mean, I spent a lot of time looking over this, and I struggled with the end results a little bit. We talked about the primary endpoint of studies when we were discussing adjuvant therapy. And one of the things we'd mentioned is that you decide on this beforehand. And the primary endpoint in this trial was actually the delay in cancer growth. And as you pointed out, the study met that endpoint. But how do you interpret the results overall? How are you incorporating triplet therapy now? Dr. Zhang: Sure. I think it did certainly meet the progression-free survival primary endpoint. The median was not reached for the triplet versus 11.3 months for the doublet. And so importantly, I think it was a, quote-unquote, "positive trial." But how are we using this? Well, we have not seen the overall survival data of these patients. And so when you're thinking about combining all 3 drugs in the frontline setting, I think it's really important to think about what might come after and whether these folks truly live longer with using all 3 upfront versus a sequential approach. So I think the jury is still out. It certainly met its primary endpoint, and it's quite promising. But I'm still waiting for the overall survival data to really inform or change my practice. Dr. Pal: I've got to agree with you there. One of the things that we always discussed in clinic is whether or not a particular treatment strategy is going to increase longevity. It comes up in every conversation, I would say, whenever we're thinking about approaching a new line of treatment. And I wish I could say definitively that this triplet strategy improves longevity, but to be totally fair, that data just doesn't exist yet. So it's a really difficult conversation. I agree with you. Maybe a little pause before we start incorporating triplets. So I've got to say, it was certainly a big year for kidney cancer, one of my fellows put this table together, and it really showed that this year amongst the past maybe 10 years in kidney cancer, we had more big phase 3 trials being reported as more than any year previously. But there are also some pretty key developments in other diseases that you and I treat, Tian, and one of those is bladder cancer. And a trial that I think was really quite important has the name EV-103. Tough name to remember, but it actually looked at a disease space that I think can be a bit of a challenge for us, and that's the patient who is presenting in the clinic has actually advanced bladder cancers spread to other parts of the body and is quite ill and perhaps can't receive conventional aggressive chemotherapy with a drug called cisplatin. So what did this proportion of EV-103 that was presented show us? Dr. Zhang: Well, people hear about Cohort K thrown around, and so this trial actually has had multiple cohorts. And this particular cohort came out of some really exciting data from their dose escalation studies, and also Cohort A, where patients were treated with an antibody drug conjugate, this enfortumab vedotin, or EV, with an immune checkpoint inhibitor called pembrolizumab. And in the early cohort of 40 patients, they saw a pretty high objective response rate. That means the rate of patients where tumors were shrinking. And so that was about 70% of those 40 patients had objective responses. And so they designed this Cohort K to randomize patients to either enfortumab vedotin with pembrolizumab or enfortumab vedotin on its own, which has been approved in refractory metastatic urothelial cancer but particularly for first-line cisplatin-ineligible patient population. And so they randomized about 150 patients in the setting and looked at objective responses, and I agree with you. Certainly, very promising in terms of having objective response rate of about 65% and compared with enfortumab vedotin on its own, which came in around 45%. It does seem that this combination has more activity than the monotherapy. Dr. Pal: Yeah. That's a great summary. And to the patients out there listening, when we talk about responses, we're talking about pretty deep responses here, meaning 30% or more reductions in the size of tumors. And Tian mentions that you've got 65% to 70% of patients with these responses. It really does entail a sizable reduction, not just a small decrease in the volume of tumors. And I'm telling you, just from having been in the scene for 15 years now, I mean, it's just remarkable sort of progress that we're making. We're going to wrap up by talking about prostate cancer, and just to really describe some overarching results. So there's a setting in prostate cancer that I always find to be a bit of a challenge, and these are patients who have had surgery for their prostate cancer. So extensively no visible spread of their disease, but they start having their PSA creep up afterwards. And there was a trial that sort of addressed that. Tian, can you give us the sort of quick and dirty summary of the study? Dr. Zhang: Sure. So we call this PSA recurrence or biochemical recurrence setting. And this trial was led by Dr. Rahul Aggarwal in the Alliance Cooperative Group. But everyone who had biochemical recurrence were randomized to receiving androgen deprivation therapy alone, which is usually our standard of care; a combination of that androgen deprivation therapy with apalutamide, which is an androgen receptor blocker; or the combination of a triplet of the androgen deprivation therapy, the apalutamide, and then an abiraterone acetate, which is a blocker of steroid synthesis in the adrenal glands. And so this trial enrolled ultimately about 500 patients and randomized them 1 to 1 to 1 to these 3 cohorts. And interestingly, the combinations of either the androgen receptor, androgen deprivation therapy with apalutamide or the triplet with combined abiraterone acetate all prolonged PSA progression-free survival compared to androgen deprivation therapy alone. So I think it was a really well-done study in the cooperative groups and helps answer some questions around intensifying treatment in that biochemical recurrent space. Dr. Pal: Yeah. These cooperative groups studies, each one of them are so critical. These are just funded by our federal government, and they really offer us a chance to really ask pure questions, so really, really important study design. And maybe in 30 seconds, let's go over this last study over here. I don't want to keep our listeners on for too long, but there was a study called PROpel. Again, you got to love these study names. So this PROpel study looked at advanced prostate cancer. So again, this is prostate cancer where the disease has spread from the prostate to other organ systems. This is potentially a new paradigm for the disease. Before, we used to just basically give everybody hormone therapy in this setting. We've doubled down and given patients more advanced hormonal therapy with drugs like abiraterone that you alluded to, but now there's this potential to use targeted treatments. And maybe you can tell us a little bit about how that's been incorporated in PROpel, Tian. Dr. Zhang: Sure. Well, PROpel randomized patients to a combination of abiraterone with olaparib, which is what we call PARP inhibitor, and it blocks DNA damage repair, basically, in cancer cells. And olaparib has been approved as a single agent in more refractory, metastatic, castration-resistant prostate cancer. And so this trial randomized folks with a combination in sort of earlier lines of castration-resistant disease to either that combination or abiraterone with placebo. We saw earlier this year, actually, that the primary endpoint was improved for all comers, but I don't know if we saw some more subgroup analysis of patients with BRCA alterations and also with homologous recombination repair alterations. And I think that's very important, the fact that we saw more of an improvement in those subpopulations than those patients without the BRCA alterations or the homologous recombination repair mutations. Dr. Pal: Excellent. Excellent summary. I think that's about all that we've got time for today. New paradigms in prostate cancer and bladder cancer potentially and a massive amount of new data in kidney cancer to things going forward with clinical practice from ESMO 2022. Tian, thanks so much for joining me today, and I hope everyone listening enjoyed this as well. Dr. Zhang: Thanks, Monty. Take care. ASCO: Thank you, Dr. Pal and Dr. Zhang. 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.

Spotlight on Kidney Cancer With Drs. Toni Choueiri and Sumanta "Monty" Pal

ASCO Daily News

Play Episode Listen Later Dec 9, 2021 22:52

Guest host, Dr. Neeraj Agarwal, ASCO Daily News editor-in-chief and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, discusses the practice-changing KEYNOTE-564 and SWOG 1500 trials with Drs. Toni Choueiri and Sumanta "Monty" Pal. Dr. Choueiri is director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute and Dr. Pal is co-director of City of Hope's Kidney Cancer Program and associate editor of Cancer.Net. (This episode was recorded on 11/18/2021) Transcript Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News podcast. I am Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, and the professor of Medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. I'm delighted to welcome two internationally recognized leaders in the field, Dr. Toni Choueiri and Dr. Sumanta (Monty) Pal, for a discussion about two practice-changing studies in kidney cancer published this year-- KEYNOTE-564 and SWOG 1500. As a quick introduction, Dr. Choueiri is the director of Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute. He's also the Jerome and Nancy Kohlberg Chair, and professor of medicine at the Harvard Medical School. Dr. Sumanta "Monty" Pal is a professor in oncology, and co-director of City of Hope's Kidney Cancer Program, and he is an associate editor of cancer.net of ASCO. Our full disclosures are available in the show notes. And disclosures relating to all episodes of podcasts can be found on our transcripts at ASCO.org/podcast. Toni and Monty, what a day it has been for our patients with kidney cancer. I woke up with the news of the U.S. Food and Drug Administration (FDA) approval of the first ever adjuvant immunotherapy for patients with renal cell carcinoma. It is so great to have you both on the podcast today. Dr. Monty Pal: Glad to be here. Thanks, Neeraj. Dr. Toni Choueiri: Thank you, Neeraj. So glad to be here. Dr. Neeraj Agarwal: So, let me start by asking questions to you first, Toni. So, you recently published the primary results of the phase 3 KEYNOTE-564 study, showing the efficacy of adjuvant therapy with pembrolizumab and immune checkpoint inhibitor in patients with renal cell carcinoma. And this study led to the approval of pembrolizumab this morning. So, please tell us more about the study design and why did you do this study. Dr. Toni Choueiri: Thank you, Neeraj. And thank you, really, ASCO for this wonderful podcast series. And a big hit, I always listen to them when I'm driving or jogging. And really, thanks for this opportunity because kidney cancer adjuvant therapy has been something like a holy grail we're trying to find for a long, long time. The first adjuvant trial, a randomized trial, in renal cell cancer was in 1973 with radiation therapy. And since that time, all the trials except for one have been a complete failure in a way. And the first adjuvant immunotherapy trial was with old immunotherapy cytokine that we don't use much anymore and was in 1992. I was not done with medical school. I was not actually done with high school at that time, let alone medical school. And now that we have, as we all know, a revolution in the oncology field through these immune checkpoint inhibitors that reinvented immunotherapy in cancer, and now that pembrolizumab has shown activity in patients with more advanced disease, we thought about taking this into the adjuvant setting, a setting of patients where they were subjected to surgery. But on the pathology report, we knew that their risk of this cancer coming back, of recurrence, is somewhat intermediate high or high. These are patients that have stage 2 but grade 4, stage 3, D3, D4. These are patients that had node-positive resected. And we took even patients where the kidney is out, but, also, they had a removal of a metastatic site--let's say a lung metastasis--within a year of removing the kidney. And we know these patients we refer to as M1NED are at quite high risk of recurrence. And we randomly assigned 994 patients to receive pembrolizumab for a year versus placebo. And after a median follow-up of only 2 years--so I want to insist here that this is short for any trial in general--we saw a decrease in the risk of recurrence or death. The hazard ratio for disease-free survival was 0.68. So, a 32% decrease in the risk of recurrence or death. We looked at safety, and we already are familiar in the field of GU oncology with pembrolizumab. And we didn't see when we looked at the safety profile any surprises, any enhanced toxicity. Of course, immune-related adverse events are the number one concern with pembrolizumab. There were no deaths on trial related to pembrolizumab. We saw around 7% of patients needing high dose steroid to medicate these immune-related adverse event, and some patients had to come off therapy for that. We also took a look, Neeraj, an early look, at overall survival. We only had 25% of events, 51 deaths. And we did not meet the very rigorous statistical significance that is needed to say that study is positive for overall survival. But the hazard ratio was 0.54, a 46% decrease in the risk of death, which is kind of encouraging. And after a year, the curve starts to separate. Before a year, they're not separating. And that is consistent with prior studies in general. Dr. Neeraj Agarwal: This is a very interesting point you just raised, that DFS, disease-free survival, is strongly positive. And even overall survival is trending in the right direction, right? Dr. Toni Choueiri: Correct. Dr. Neeraj Agarwal: That's great. So obviously, I would like to raise another point here. When we talk about adjuvant study, we usually think about a localized kidney cancer, which is removed by the surgeon, and then [the] patient is coming to see us for treatment in adjuvant setting. But this study, I would like to highlight, as you said, also included patients who had oligometastatic disease, had successful surgical removal of the oligometastatic disease, and they were also eligible for this trial. Dr. Toni Choueiri: Yes, absolutely. And I think this is somewhat on the recent side in clinical trials in kidney cancer. The reason for that is that, in practice, we see those patients. And we even had two small trials in the TKI era with sorafenib and pazopanib, small studies, were also completely negative. So, we thought here that we should not exclude these patients. They end up being 6%, 7% of all participants, but this remains an area of unmet medical need. Dr. Neeraj Agarwal: So, how is the hazard ratio in those patients who had metastatic disease removed and then treated with pembrolizumab? Dr. Toni Choueiri: Yeah, it was very low. It was 0.2, so 0.29. And this was great to see. I don't want to go into really over-interpreting these results. All the hazard ratio--when you look at subgroup analysis or in the forest plot, all the hazard ratio are less than 1. We didn't see something--let's say 1.5--in favor of pembrolizumab. Now you go into a smaller subgroup, then your confidence intervals are very large and hard to interpret, except that to say, look, on average there could be a significant benefit here, but we can't tell. Dr. Neeraj Agarwal: Sure, absolutely. I agree with you. So, how this is going to affect the current treatment paradigm, which is for patients with newly diagnosed metastatic RCC, where combination of VEGF-TKI plus immunotherapies (IOs) or IO/IO combinations have become standard of care or treatment paradigm? Dr. Toni Choueiri: I do believe it will be a standard of care currently in the right population. There are a lot of unanswered questions, but that will be answered hopefully with more follow up. We have already, beside these results, reported--so these results were reported in the plenary session at the 2021 ASCO [Annual Meeting]. But later on, another analysis dealing with patient-reported outcome and quality of life was reported at ESMO and also showed no detriment in quality of life--that's the voice of the patient--no detriment with pembrolizumab (pembro). There is a lot still to do and a lot of unanswered questions, such as the non-clear cell histology, those patients who had surgery of their metastatic disease more than a year. But most important, I think, two questions. One, how can you know from the get-go who are the patients that need adjuvant pembrolizumab? We do not have any valid ctDNA. And I know Dr. Pal was involved with a lot of these type of research. We don't have any ctDNA test that is really that faithful and sensitive in the MRD space in renal cell. Many of us are working, so we don't know. We may end up over-treating patients that need surgery only. And actually, we may end up under-treating patients that need, perhaps, pembro, and another drug. And the second thing in those patients--and I hope it does not happen, but unfortunately, it will to some extent--whose tumor progress on adjuvant pembrolizumab, what do you do? What's the treatment paradigm? And actually, there is no data. This is a data-free zone. And I would think somebody whose tumor progressed, tumor continued to grow or grows, while they're actively on pembrolizumab, on IO, is way different than someone whose tumor comes back after 2 or 3 years from stopping the drug. Should we treat them with the same drug? Should we treat them with the TKI plus IO? Luckily, there are trials that are ongoing in patients whose tumor progressed after PD-1/PD-L1 inhibitor to give them a TKI as a control arm, or a TKI plus an immune checkpoint inhibitor. And I know Dr. Pal is very heavily involved with such trials. So, hopefully, we will answer this question, but not anytime soon. Dr. Neeraj Agarwal: Very interesting, and definitely new results are posing new challenges in how we practice medicine here in the coming future. So, Monty, you are leading a trial with a very similar trial with atezolizumab. And I'm really hoping, we are all really hoping, that we see the other trial being positive, so we have more treatment options for our patients. Dr. Monty Pal: I couldn't agree with you more. I mean, I definitely think that Toni's study really adds a lot of fuel to the fire suggesting that this strategy of adjuvant immunotherapy may be successful in localized renal cell. Dr. Neeraj Agarwal: And I'm not going to really delve into the side effects of pembrolizumab and atezolizumab because these drugs are used quite often. They are in widespread use for different types of cancer. But just a quick question, any safety signal, Toni? Did you see any safety signal with pembrolizumab in this patient population? Dr. Toni Choueiri: Yeah, this is an excellent question. So, nothing that would be different than using pembrolizumab overall knowing in other diseases as a single agent. So, this drug not first in human, as you know, and it's been approved in combination or as a single agent in many diseases. A tumor that the three of us treat is bladder cancer, and we know from another study how to use pembrolizumab. I think that the use of corticosteroid is somewhat of an objective way, at least to me, in looking at immune-related adverse event. And it has been between 5% to 10%, so we're not way off here. But there is no doubt that there are patients that we had no death on trial attributed to drug that may have, with pembrolizumab, some serious toxicities. We had patients that had autoimmune diabetes, hypophysitis, pneumonitis--quite uncommon, but not impossible. Dr. Neeraj Agarwal: We'll still need to keep an eye for that, basically. Dr. Toni Choueiri: No doubt. Dr. Neeraj Agarwal: Yes. So, changing gears, let's talk to you, Monty. You recently presented the primary results of the SWOG 1500 trial in patients with metastatic non-clear cell renal cell carcinoma. Could you please tell us why you did this study and how this study's design was unique compared to similar studies in this setting? Dr. Monty Pal: Yeah. No, absolutely. Toni did a great job of outlining areas that are sort of free of data in the adjuvant space, particularly with immunotherapy. I think that data-free area for us in kidney cancer for a long time has been non-clear cell histology. We just don't really know how to treat them. And I actually got advice from Toni when I was devising SWOG 1500. We planned it out as a very simple study comparing sunitinib and cabozantinib. And Toni will remember this history well. It sort of went through several iterations. The study blossomed into a six-arm trial. Ultimately, it turned into a four-arm study, looking at sunitinib versus cabozantinib versus two other MET inhibitors--savolitinib and crizotinib. And ultimately, the study was boiled down to essentially what we'd originally proposed. Two of the MET inhibitors--savolitinib and crizotinib--failed to surpass that initial analysis for PFS. So, ultimately, we demonstrated a superiority with cabozantinib over sunitinib for progression-free survival. Dr. Neeraj Agarwal: So, what is the current treatment paradigm for patients who have newly diagnosed metastatic papillary RCC now? Dr. Monty Pal: I think for patients who don't have genomic selection, I think that cabozantinib remains the standard. I really want to champion- and maybe Toni can talk a little bit more about this--a study that Toni is leading called the SAMETA trial, which I think has a really innovative design. And it's going to be genomically characterizing patients and randomizing to savolitinib with durvalumab or sunitinib. Tell me, Toni, if I have the design right there. Dr. Toni Choueiri: Yes. Actually, this is a specific study in a specific population. It's not in papillary RCC as much as in those 30%, 40% of papillary RCC that have MET-driven tumors, so MET alteration, whether through chromosome 7 duplication, through chromosome 7 trisomy, through mutation or amplification. These patients will get either control arm or they will get savolitinib, which is a pure MET inhibitor that is devoid of VEGF-related toxicities, savolitinib plus durvalumab, or durvalumab alone. So, two experimental arms and one control. And the reason for this is we saw activity and quite a good toxicity profile with savolitinib, a pure MET inhibitor, over sunitinib in an earlier trial that was sunitinib against savolitinib in selected patient populations. The study had to close early. So, despite the numerical difference, this was not statistically significant. And then in another study led by Dr. Powles and colleagues, there was also some interesting activity how durvalumab could augment that activity. So, we're launching a phase 3 trial with three arms that you described very well. Dr. Neeraj Agarwal: That's wonderful. So, what are the next steps, Monty? I mean, this is amazing to see you designing an investigator-initiated trial. This was your concept. You designed it. You built this to be a huge multicenter trial, which was open across the country, funded by the National Cancer Institute. And congratulations for making that happen. It's rare for us to see these trials going from a concept stage to a national trial, and then changing the standard of care. So, what are the next steps now for you and your team in SWOG for papillary RCC or metastatic papillary RCC? How do you build out further with the backbone of cabozantinib? Dr. Monty Pal: I really appreciate the question, Neeraj. It's so critical to understand that we're just not quite done yet. Toni's study, as I've mentioned, is incredibly innovative. I'm also really thrilled to be working with someone who you've mentored so well, Ben Maughan, at the Huntsman Cancer Institute in Utah. And he's actually designed a brilliant study, which we're going to be leading together, which looks at cabozantinib with or without atezolizumab. Recently, in a study that you and I and Toni were a part of that we just published in JCO, we actually saw quite impressive response rates with the combination of cabozantinib and atezolizumab in patients with papillary RCC, around 47%. Those response rates were actually replicated in a separate study run by Joe Lee at Memorial Sloan Kettering. In the context of papillary disease response rates were again above a threshold of around 40%. So, I think there's something to it. But until we really subject this to randomization, I think we're not going to know whether or not cabo plus IO is standard. So, I encourage everyone to consider Toni's study. I encourage everyone to look out for our trial of cabo plus or minus atezo, which should be rolling out next year. Dr. Neeraj Agarwal: What is the name of the trial, or the number, for our audience? Dr. Monty Pal: Yeah, we lucked out with another great number. We got 1500 for the first trial. This is going to be SWOG 2200. So SWOG 2200, and I think it's due to open maybe in the first quarter of 2022. Dr. Neeraj Agarwal: That's fantastic news. Any new signal? We know cabozantinib is already approved for our patients with metastatic RCC, courtesy METEOR trial led by Dr. Choueiri. Toni, it's amazing to see how many times you have changed standard of care for our patients with metastatic RCC. So, any new safety signal of cabozantinib in this patient population with metastatic papillary RCC? Dr. Monty Pal: Nothing that appreciated. The toxicity profile was pretty much on par with what you'd anticipate for cabozantinib in the setting. Major side effects were hypertension, hand-foot syndrome, [and] diarrhea. Nothing that really sort of stood out relative to what we would expect in a clear cell population of patients. Dr. Neeraj Agarwal: That's great. Any final messages for our patients, for our audience, for our listeners? Dr. Toni Choueiri: Well, let me start, and maybe Monty can add. It's been, and it hopefully will continue to be, this humbling experience, where median survival from metastatic RCC in mid-2000--not long time ago during our training--has been 1 year. And now in metastatic disease, it's 4 to 5 years. And that is only going to get better. And then it's even more humbling to be in a time where you can talk about adjuvant treatment in this disease, renal cell cancer, that continues every year to kill, unfortunately, 14,000 Americans. That's just in the U.S. alone. So, we have to continue in getting more targets, more drugs, more reasonable combination, and the right patient, whether through specific biomarker that are tissue or blood-based or specific liquid biopsies that can tell you who has and who doesn't have cancer at the microscopic levels. Dr. Neeraj Agarwal: Thank you. How about you, Monty? Any final message for our audience? Dr. Monty Pal: I couldn't have summarized it better than Toni, just such a wonderful statement around optimism for what we've achieved so far and what's yet to come. And if I could emphasize to anyone in the audience today the need to keep progressing the field further with clinical trials, I think that would be my underlying message. Dr. Neeraj Agarwal: Thank you again, Toni, Monty, for your valuable insights and thoughts. Thank you for all the inspiration. This is indeed so inspiring to see your work, which is changing the lives of our patients on a daily basis. Our listeners will find links to your studies in the transcript of this episode. I wish you all the best. Dr. Toni Choueiri: Thank you. Dr. Neeraj Agarwal: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you so much. Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Pfizer, Merck , Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Foundation Medicine, Gilead Sciences Research Funding (inst.): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas Dr. Sumanta (Monty) Pal: Consulting or Advisory Role: F. Hoffmann LaRoche, F. Hoffman Research Funding (inst.): Eisai, Genentech, Roche, Exelixis, Pfizer Travel, Accommodations, Expenses: Genentech, Seattle Genetics Dr. Toni Choueiri: Employment: Dana Farber Cancer Hospital Leadership: Dana Farber Cancer Hospital, NCCN, KidneyCan, ASCO, ESMO Stock and Other Ownership Interests: Pionyr, TEMPEST Honoraria: NCCN, UpToDate, Michael J. Hennessy Associates, ASCO, Harborside Press, Analysis Group, AstraZeneca, Alexion Pharmaceuticals, Sanofi/Aventis, Bayer, Bristol-Myers Squibb, Genentech/Roche, GlaxoSmithKline, Merck , Novartis, Peloton Therapeutics , Pfizer, Corvus Pharmaceuticals, Ipsen, Foundation Medicine, Eisai, PlatformQ Health, Clinical Care Options, Navinata Healthcare, Kidney Cancer Journal, Exelixis, Prometheus, Lpath, NEJM, Lancet Oncology, Cerulean Pharma, alligent, EMD Serono, HERON, Lilly, Janssen Oncology, IQvia, Aveo, and NCI. Consulting or Advisory Role: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Exelixis, Prometheus Laboratories, alligent, Ipsen, Corvus Pharmaceuticals, Lpath, Alexion Pharmaceuticals, Sanofi/Aventis, Peloton Therapeutics, UpToDate, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Journal, Clinical Care Options, Paltform Q, Navinata Healthcare, Harborside Press, ASCO, NEJM, Lancet Oncology, EMD Serono, HERON, Lilly, ESMO, NiKang Therapeutics, Kanaph Therapeutics, Infinity Pharmaceuticals, and Aravive Research Funding (inst.): Pfizer, Novartis, Merck, Exelixis , TRACON Pharma, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Peloton Therapeutics, Roche/Genentech, Celldex, Agensys, Eisai, Takeda, Prometheus, Ipsen, Corvus Pharmaceuticals, Cerulean Pharma, Seattle Genetics/Astellas, Bayer, Foundation Medicine, Roche, Calithera Biosciences, Analysis Group, NCI, GATEWAY for Cancer Research, and Congressionally Directed Medical Research Programs (DOD) Patents, Royalties, Other Intellectual Property (inst.): International Patent Application No. PCT/US2018/058430, entitled “Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy, International Patent Application No. PCT/US2018/12209, entitled “PBRM1 Biomarkers Predictive of Anti-Immune Checkpoint Response Patents, Royalties, Other Intellectual Property: ctDNA technologies Travel, Accommodations, Expenses: Pfizer, Bayer, Novartis, GlaxoSmithKline, Merck, Bristol-Myers Squibb, Roche/Genentech, Eisai, Foundation Medicine, Cerulean Pharma, AstraZeneca, Exelixis, Prometheus, alligent, Ipsen, Corvus Pharmaceuticals, Lpath, Alexion Pharmaceuticals, Sanofi/Aventis, UpToDate, Peloton Therapeutics, NCCN, Michael J. Hennessy Associates, Analysis Group, Kidney Cancer Journal, Clinical Care Options, PlatformQ Health, Harborside Press, Navinata Healthcare, NEJM, Lancet Oncology, EMD Serono, HERON, Lilly, and ESMO Other Relationship: Medical writing and editorial assistance support may have been funded by Communications companies funded by pharmaceutical companies such as ClinicalThinking, Health Interactions, Envision Pharma Group, Fishawack Group of Companies, Parexel Disclaimer: 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.

university americans travel food medicine cancer utah companies ios consulting benefit pfizer gateway keynote drs gu harvard medical school io astrazeneca pd pal bayer prometheus monty roche merck meteors dfs d3 heron janssen cancer research michael j novartis royalties accommodations biomarkers uptodate asco genentech amgen national cancer institute mrd glaxosmithkline drug administration fda bristol myers squibb takeda dana farber cancer institute nejm rcc d4 pfs nci memorial sloan kettering nektar vegf iqvia pd l1 ipsen kidney cancer esmo tki eisai joe lee jco asco annual meeting nccn huntsman cancer institute ctdna emd serono sanofi aventis foundation medicine aveo alexion pharmaceuticals analysis group parexel swog choueiri seattle genetics roche genentech arvinas pharmacyclics janssen oncology transcript dr disclosures dr neeraj agarwal toni choueiri sumanta monty pal mei pharma

Clinical Trials in Genitourinary Cancers: KEYNOTE-641, P3BEP, PIVOT-09

Play Episode Listen Later Aug 20, 2020 17:54

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, germ cell, and kidney cancer. This podcast will be led by Dr. Sumanta (Monty) Pal, Dr. Neeraj Agarwal, Dr. Timothy Gilligan, and Dr. Tian Zhang. 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 Astellas Pharma, and 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 Astellas Pharma, Bristol-Myers Squibb, Nektar Therapeutics, and Merck. Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Center. He has no relevant relationships to disclose. 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 Bristol-Myers Squibb and Merck. View full disclosures for Dr. Pal, Dr. Agarwal, Dr. Gilligan, and Dr. Zhang at Cancer.Net. Dr. Pal: Hi. I'm Dr. Monty Pal from the City of Hope. I'm joined today by Dr. Neeraj Agarwal from the Huntsman Cancer Institute and University of Utah, Dr. Timothy Gilligan from the Cleveland Clinic Taussig Cancer Institute, and Dr. Tian Zhang from Duke Cancer Institute. Today we're going to discuss 3 ongoing clinical trials in prostate, germ cell, and kidney 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 a 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's 2020 Genitourinary Cancers Symposium. 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 visit the show notes for the episode on Cancer.Net. Now, the first trial we're going to discuss is the KEYNOTE-641 trial for prostate cancer. [Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641)] Dr. Agarwal, can you tell us who this study is designed for? Dr. Agarwal: This trial is designed for patients with advanced prostate cancer, or metastatic prostate cancer, who are experiencing disease progression on standard androgen deprivation therapy, a state known as castrate resistant prostate cancer. Dr. Pal: And if you see these patients in your clinic right now, what is the current standard of care? Dr. Agarwal: The most commonly utilized [treatments for] these patients include drugs which block androgen signaling inside the prostate cancer cell. And one of the most commonly utilized drugs is enzalutamide followed by abiraterone. Dr. Pal: Tell us a little bit about how this particular study aims to improve or change the current standard of care. Dr. Agarwal: Early clinical data showed that adding the immunotherapy agent pembrolizumab to enzalutamide may improve survival outcomes. The response rates in that smaller study were meaningful and were very promising. Based on those earlier data, this trial has been designed and is asking two main questions. Number one, whether adding the immunotherapy agent pembrolizumab to enzalutamide will improve overall survival. And the second question is, whether adding pembrolizumab to enzalutamide will delay disease progression. Dr. Pal: Are there any risks that patients should be aware of with this regimen? Dr. Agarwal: Both agents are very commonly utilized for many years now in oncology clinics. Enzalutamide is an oral pill which blocks androgen signaling and is associated with side effects such as fatigue, muscle loss, bone loss, falls, and many others which are relatively easy to manage over time. Pembrolizumab is an intravenous therapy approved for multiple cancer types, and is associated with immune-related side effects. Many of these can be severe in 4 to 5 percent of patients receiving pembrolizumab. These can include diarrhea, abnormal liver function tests, or liver toxicity, a skin rash, lung toxicity, which can include pneumonitis [or lung inflammation]. But most of these side effects can be managed as long as they are promptly detected. So I think education and close monitoring with oncologists is the key for early prevention and management of the side effects. Dr. Pal: Those are great tenets, not just for this clinical trial but in using these agents in general. Thanks a lot. And final question for you, Dr. Agarwal. Is this trial still open right now? And if so, when do you think we might see some results from it? Dr. Agarwal: This trial is open across the United States and different parts of the world. And the primary results, early results, will be available, I'm hoping, in 2023, in the middle of 2023. Dr. Pal: Well thank you for that excellent overview, Dr. Agarwal. I'm going to turn my attention now to Dr. Gilligan to discuss a topic that we don't often have on this podcast. But this is nonetheless a critical disease space for us to discuss. Dr. Gilligan is going to tell us about the P3BEP clinical trial in testicular cancer. [Accelerated v's Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours (P3BEP)] Dr. Gilligan, can you tell us a little bit about who this study is designed for? Dr. Gilligan: Yes, germ cell tumors are cancers that start in the reproductive cells, most commonly in testicles of adolescent or adult men. But germ cell tumors can also start in children - typically not in the testicles but elsewhere in the body - and they can start in women in the ovaries or elsewhere. In children, we sometimes see [germ cell tumors starting in the brain]. Those are not included in this trial. But basically, everybody else with germ cell tumors are eligible for this - men, women, and children - if they have a poor or intermediate prognosis. And just to clarify one more piece about that, this is for people who have advanced stage disease. Again, men, women, or children with advanced stage metastatic germ cell tumors, as long as it didn't start in the brain. And as long as their prognosis is in the intermediate or poor risk category, not the good risk category. Dr. Pal: So glad that you pointed that out, Tim. I have to tell you that I gave this incorrect label of a testicular cancer study, but critical for our listenership to know the germ cell tumors can occur both in males and females. Can you tell us a little bit about the current standard of care for the patients that are being [included] in this study? Dr. Gilligan: Absolutely. Chemotherapy for germ cell tumors has been one of the huge success stories of modern oncology, and the cure rate is extremely high. Overall, [we cure about 96% of men with testis cancer.] However, when you start to look at advanced stage disease in intermediate and poor risk patients, the success rate goes down. It's about a 75% cure rate for patients with intermediate risk tumors and 60% for [those with] poor risk tumors. The standard of care has been the same for a long time. It's 4 cycles of chemotherapy called BEP, and that's what has produced those results. And while those results are good, we would like them to be a lot better. Dr. Pal: So Dr. Gilligan, you've used this term intermediate and poor risk in the context of patients with germ cell tumor. Can you tell us a little bit about what intermediate and poor risk [means]? Dr. Gilligan: Yes, it's based mostly on where the cancer has spread to and how high certain blood tests are. There are things called tumor markers which are proteins in the blood that are made by the cancer, and the higher those levels, the worse the prognosis. Similarly, if the cancer has spread to certain organs, such as the liver or the bones or the brain, organs other than the lungs, then patients have a poorer outcome and a poorer prognosis. The last category is men and women who have certain germ cell tumors that grow in the chest called extragonadal tumors. They also have a prognosis that's not as good as other germ cell tumors. So it's a little bit complicated, and for patients, when you see your oncologist, they can clearly tell you which prognostic category you fall into. Dr. Pal: How does this study aim to improve or change the standard of care? Dr. Gilligan: So mainly we'd like to get those numbers better. And I think the key idea in this study is that with chemotherapy, which is different than the kinds of drugs we talked about in the prior conversation, the philosophy is to basically give patients as much of a dose as they can safely tolerate. And the idea of this trial is that if we give the chemotherapy more frequently - if we kind of squeeze together the cycles so that rather than every 3 weeks we're repeating it every 2 weeks - can we get a better response in killing the cancer without having too much toxicity? Dr. Pal: So they use this term in the title “accelerated.” Is that what you're referring to there? Dr. Gilligan: Yes. So if you think of chemotherapy as something that is repeated, we're repeating it sooner. And we used to give the patient 3 weeks to recover. On this trial, they're comparing that standard approach every 3 weeks to giving it every 2 weeks. In other words, we're making it denser. You get the chemotherapy faster. And the question is, will we cure more people that way or not? Dr. Pal: And Dr. Gilligan, any known risks that patients should be aware of as they [consider] a study like this? Dr. Gilligan: Well I think the risk with this approach is that we may increase toxicity without improving outcomes. Past attempts to do better than the standard treatment have not been successful. And the current standard treatment has been the standard for a long time as a result. We are hoping the new approach will be better, but we don't know until we try it, and it's possible that it will be more toxic. Dr. Pal: When do you think we might see some results from this? Dr. Gilligan: I don't know when we will see results. My guess is that it will be within a few years. Germ cell tumors grow quickly; they're aggressive cancers, so you tend to get your results pretty quickly, but I don't know exactly. Dr. Pal: Dr. Gilligan, thank you for that excellent overview. Last, but certainly not least, we're going to turn our attention to Dr. Tian Zhang for discussion of a very important study in kidney cancer. [A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)] Tell us a little bit about this study and who it's designed for. Dr. Zhang: PIVOT-09 is a study of a combination of a [novel] immunotherapy called bempegaldesleukin in combination with nivolumab compared to investigator-selected sunitinib or cabozantinib. So these are standard blood vessel blockers. The study is designed for patients with metastatic clear cell kidney cancer who have had no prior medication treatments and also measurable disease that can be followed on subsequent scans. Dr. Pal: And when you're seeing these patients in clinic with metastatic kidney cancer, what is the current standard of care? What are you using to treat patients these days? Dr. Zhang: We've known for a long time that kidney cancer will respond to these immune activating therapies, and [it has been demonstrated that a drug called IL-2, when given in high doses,] improved the overall survival for a subset of patients with metastatic kidney cancer and [produced] really durable complete responses for a small number of patients. However, it was highly, highly toxic, and there were lots of patients who ended up in the hospital. It had significant toxicities and patients were treated in the hospital for about a week at a time. So since about 2018, our standard of care immunotherapy options [have included] agents like ipilimumab and avelumab or the combination of pembrolizumab or avelumab with a blood vessel blocking agent. This is an easier way to give immune activating treatments in a more targeted fashion. [With this study we are testing] whether the IL-2 cytokine can be modified and given more in a more safe and effective manner. Dr. Pal: This is an interesting drug. If I understand it correctly, we're taking IL-2 from yesteryear, a drug that we used more than a decade ago to treat patients with advanced kidney cancer, and we're retooling it a bit for patients to really enhance the efficacy, maybe really enhance the safety of the compound as well. Can you tell us how this compound's doing that? Dr. Zhang: Right so bempegaldesleukin is a special formulation of IL-2. It's actually a pegylated form of the IL-2 cytokine, so it includes this polyethylene glycol molecule around the IL-2. And this pegylation allows that cytokine to be released slowly [in the bloodstream] so that in itself may improve the side effect profile. And then it also activates the tumor fighting subset of immune cells, T cells and natural killer cells in the tumor microenvironment, without activating other suppressive T cells. So the thought from preclinical studies is that bempegaldesleukin, because of its pegylated form, will actually decrease the side effects while activating the tumor fighting cells in the tumor microenvironment. Dr. Pal: And in this trial, how will success be evaluated? How will we know the treatment is working, that it's positive? Dr. Zhang: So the primary objective for this particular trial is a composite of objective responses as well as overall survival, and then secondary objectives include progression free survival - so lengthening time until disease progression - as well as evaluating the safety of the combination and the quality of life for patients who are treated on this combination. Dr. Pal: Now I remember IL-2, the drug that you referred to, from more than a decade ago, giving it to patients and certainly it came with a lot of toxicity. What are some of the toxicities of patients receiving bempegaldesleukin should be aware of? Dr. Zhang: Some of the early phase 1 trials that evaluated bempegaldesleukin found that some of the toxicities included low blood pressure as well as syncope where patients would feel lightheaded [or faint,] headaches, edema, swelling in their legs and fluid buildup, as well as infusion reactions. And I think we should also think about the immunotherapy-related toxicities of nivolumab where we're giving it in combination. So diarrhea, rashes, endocrine dysfunction are pretty common. So those would be some of the expected side effects of the immunotherapy cohort. And then we shouldn't forget about the control cohort treated with standard sunitinib or cabozantinib, and those side effects would include hypertension, hand foot syndrome or other rashes, diarrhea, nausea, hypothyroidism, and loss of protein in the urine. Dr. Pal: Right. Well a final question for you Dr. Zhang. Is this trial still open to patients, and if it is, when do you think we might see some results from it? Dr. Zhang: Yes, the trial is still open. It's enrolling up to 600 patients total and it's currently open globally in the U.S., Mexico, South America, Asia, Russia, and Australia. I'm hoping we will see results from this phase 3 trial in the next 2 to 3 years. Dr. Pal: Well thank you very much, Dr. Zhang, Dr. Gilligan, Dr. Agarwal. 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. Thanks so much for listening. ASCO: Thank you, Drs. Pal, Agarwal, Gilligan, and Zhang. 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.

united states university australia mexico russia medicine study cancer utah poor patients associate professor south america google play pivot keynote drs american society investigators pal germ zhang clinical trials merck accelerated chemotherapy agarwal asco bristol myers squibb duke university school clinical oncology bep medical oncologist genitourinary pembrolizumab huntsman cancer institute conquer cancer i'm dr duke cancer institute genitourinary cancers symposium sumanta monty pal asco podcast network

Clinical Trials in Genitourinary Cancers: TALAPRO-2, KEYNOTE-905, COSMIC-313

Play Episode Listen Later Jul 9, 2020 25:49

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. Sumanta (Monty) Pal, Dr. Petros Grivas, and Dr. Tian Zhang. Dr. Gilligan is an Associate Professor and Medical Oncologist at the Cleveland Clinic Taussig Cancer Center. He has no relevant relationships to disclose. 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 Astellas Pharma, Exelixis, and Pfizer. 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 Exelixis, Merck, and Pfizer. 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 Exelixis, Merck, and Pfizer. View full disclosures for Dr. Gilligan, Dr. Pal, Dr. Grivas, and Dr. Zhang at Cancer.Net. Dr. Gilligan: Hi. I'm Dr. Timothy Gilligan from the Cleveland Clinic. I'm joined today by Dr. Monty Pal from the City of Hope Cancer Center, Dr. Petros Grivas from the Fred Hutchinson Cancer Research Center and University of Washington, and Dr. Tian Zhang from Duke Cancer Institute. Today, we're going to discuss three ongoing clinical trials in prostate, bladder, and kidney cancer. As you may know, clinical trials are the main way the doctors are able to find better treatment for cancer and other diseases. Patient participation is vital for clinical trials. By participating in a clinical trial, you can directly help researchers develop better treatment, reduce side effects, or even reduce the risk of cancer all together. The three trials we'll discuss today were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers Panel from the trials and progress abstracts that were presented at ASCO's 2020 Genitourinary Cancers Symposium. 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 visit the show notes for this episode on Cancer.Net. So to get started, the first study we'll discuss is the TALAPRO-2 trial for prostate cancer, [Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC (TALAPRO-2)] and Dr. Pal is going to discuss this. So if we could get started, just to begin with, who is the study designed for? Dr. Pal: Thanks a lot, Dr. Gilligan. Well, this study addresses a unique disease population. It's patients with prostate cancer that's metastatic, and that implies that the cancer has migrated out of the prostate to other organs. But beyond that, it also implies that these patients have also developed some resistance to first line hormone treatment. So patients in this study [have] so-called hormone resistant or castration resistant [prostate cancer]. Dr. Gilligan: So if a patient was in this situation, and they weren't going on this trial, what would be the standard treatment for them at this time? Dr. Pal: There are several options for these patients. Hormone therapies like abiraterone and enzalutamide could be considered. Chemotherapy is also a consideration. Dr. Gilligan: And can you say a little bit more about what the patients would receive if they went on it? The subjects of the study, what they'll get? Dr. Pal: Some patients with prostate cancer may have [a deficiency in their cancer’s ability to repair damage to DNA]. This is something that we've seen in other tumor types, breast cancer perhaps being the most notable example. Pancreatic cancer being another one. In this particular trial, [the researchers] try to exploit that by using a class of drugs called PARP inhibitors. In this case, a drug called talazoparib. So patients in this study receive a standard hormone therapy called enzalutamide. And they receive that with or without this drug, talazoparib. Dr. Gilligan: So they will get either-- what you described before is the standard of care—hormonal therapy, or that combined with this new drug. Dr. Pal: That's exactly right, Dr. Gilligan. Dr. Gilligan: I wanted to make that clear because this is a trial that has placebo, and sometimes research [participants] have concern about, "Do I want to be on a trial that has a placebo?" Do you want to say anything about that? Dr. Pal: It's very important to bear in mind that every patient that enrolls in this study is going to get the standard treatment in this setting. As I've mentioned before, enzalutamide represents one of those options. And, of course, in this trial above and beyond that, they have the possibility of getting talazoparib or a placebo. So certainly patients won't be receiving placebo alone in this trial. Dr. Gilligan: Do you want to say anything more about what's kind of interesting about this new approach to treating prostate cancer? Dr. Pal: What I think is quite inventive about this study is that talazoparib, the PARP inhibitor, is being combined with hormone therapy. And I think that's the real difference in what this protocol offers versus the treatment strategies that now represent a standard option for patients. Dr. Gilligan: Right. And my understanding is that the hope is that by using this combination, we'll be able to make treatment more effective. Dr. Pal: Absolutely. When we talk about PARP inhibitors and prostate cancer currently, we're typically restricting it to patients who have these so-called DNA damage repair mutations. And that's certainly a finite group of individuals. In this particular trial, we're actually going to look not just at those patients, but all patients within this disease state. So we go beyond the 25 to 30 percent of patients who are estimated to have alterations in DNA damage repair. Dr. Gilligan: Right. I think that's an important point: to get on this trial, patients don't have to have a particular genetic profile. So how will success be evaluated? How will we know if it's working? Dr. Pal: In this case, we're going to be looking at the delay in cancer growth as the primary outcome measure. We're certainly hoping that the combination of enzalutamide with talazoparib is going to slow growth relative to enzalutamide plus placebo. The innovative endpoint that's explored in this study is also diving deeper and looking at those patients who have these DNA damage repair mutations that's going to also reflect one of the primary outcome measures in this study. And that's something quite important to bear in mind. Dr. Gilligan: So we have some experience with PARP inhibitors. Can you say something about what we know about the side effects? Dr. Pal: Fatigue is a relatively common side effect. Decreases in blood counts is another potential side effect. And in particular in my clinical experience, I've seen drops in the white blood cell counts. That of course makes patients more susceptible to infection. Diarrhea may also be one of the consequences within this class of drugs. And certainly, I would refer patients to a more comprehensive discussion of these side effects with their clinicians before entering into the study. Dr. Gilligan: Is the trial still accruing patients? And do we know when we might expect results? Dr. Pal: I think that there are many trials within this particular space. This one is ambitious in that it hopes to accrue over a thousand patients. I don't have a good finger on the pulse of when results will report. But I'm sure that'll be the subject of future podcasts for us. Dr. Gilligan: Well, thank you very much Dr. Pal. It's a very exciting study and exciting new area of research in prostate cancer. Dr. Pal: Definitely. Dr. Gilligan: We're going to move on now to the second study we want to talk about, which is the KEYNOTE-905 study. [Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Cisplatin-ineligible Participants With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303)] And Dr. Grivas is going to talk to us about that. Can you orient us, Dr. Grivas, to what this study is, for which group of patients, and what it's looking at? Dr. Grivas: This clinical trial is applicable to patients with localized, meaning not spread, bladder cancer. And when the bladder cancer has invaded the muscle layer of the bladder, we call this muscle invasive bladder cancer. And these patients usually go for cystectomy, the removal of the bladder. And ideally, they get chemotherapy before, but some patients may not be fit enough for chemotherapy. So those patients go straight to cystectomy, the removal of the bladder. So this clinical trial is trying to evaluate whether immunotherapy with this drug, called pembrolizumab, helps these patients before they get the cystectomy. Dr. Gilligan: Can you tell us a little bit more about pembrolizumab and what we know about it? Where it's used currently in bladder cancer? Dr. Grivas: Pembrolizumab has three different indications for patients with bladder cancer. The first one is in an earlier stage, what we call non-muscle invasive bladder cancer, which is a very superficial cancer, when the cancer is not invading through the muscle layer. And there's a specific indication for those patients who get therapy with BCG, which is a form of immunotherapy given inside the bladder. And if the cancer is not responding well to this BCG, usually, they go for removal of the bladder. But some of them may not be able to do that or do not want that. And pembrolizumab has a track record in those specific scenarios of BCG-unresponsive tumors as we call them for those patients who cannot get cystectomy or don't want to have it. The other two indications are for patients who have metastatic, [meaning bladder cancer that has spread to other organs.] And there are two specific indications of pembrolizumab immunotherapy in that particular setting. So this trial is trying to expand upon the role of pembrolizumab in bladder cancer. Dr. Gilligan: So it's been shown to be a benefit when the disease is more advanced and now we want to see if it's helpful earlier on in the period of time around surgery. Dr. Grivas: Right. And it's interesting in a particular setting we're looking at this trial, because we have indications literally before and after in an earlier states, the non-muscle invasive disease setting. And also as you mentioned, Dr. Gilligan, in the more advanced setting. So we're trying now to see whether this middle setting of muscle invasive bladder cancer, whether there's a role of pembrolizumab by itself before removing the bladder. Dr. Gilligan: Are patients who are eligible to get chemotherapy prior to cystectomy able to go on this trial or is it only for patients who are not [well enough] to get chemotherapy? Dr. Grivas: This is for patients who are not in good condition to undergo chemotherapy. So if someone is in good condition to undergo chemotherapy, then the trial does not apply to them. This is only in those who cannot safely receive chemotherapy before the cystectomy. Dr. Gilligan: Thank you for clarifying that. What data do we have that makes us think that it may be a good idea to give immunotherapy prior to cystectomy? Because this has been looked at a little bit already, and I think it's why this trial is being done. Can you say a little bit about that? Dr. Grivas: Sure. I would like to underline that as you alluded before, the standard of care therapy for patients who undergo cystectomy, the removal of the bladder, is to undergo chemotherapy with a drug called cisplatin before cystectomy. But as we discussed before, this is the standard of care with a high evidence. However, many patients, maybe 50, maybe 55 percent of patients may not have enough condition to undergo this chemotherapy safely. And that is the population we would try to capture. And to answer your question, there have been so far, four clinical trials looking at immunotherapy before cystectomy. And all of those four clinical trials look very promising in that regard. So based on this promising information, this new trial the KEYNOTE-905 is a phase III trial trying to confirm the promising data from the previous phase II trials and help us make a final decision whether this should be the standard of care or not in patients who cannot undergo safely chemotherapy in that setting. Dr. Gilligan: What are the known side effects and risks of immunotherapy? Dr. Grivas: Immunotherapy overall is much better tolerated than chemotherapy. However, it can still cause significant side effects, especially in a small proportion of patients. So the main thing we need to keep an eye on is if the immune system gets too overstimulated, it can cause what we call immunotherapy-related adverse events or side effects. And any organ of the body could in theory be attacked by an overstimulated, overactive, immune system. So they are different forms of “-itis.” For example, if you have inflammation in the lungs, it's pneumonitis. In the liver, hepatitis. So we have to be careful and educate our patients, educate our medical providers and the teams, follow the patients and then report any new symptoms for changes in order to be able to recognize early and manage properly these side effects. As I mentioned, it's not common to have a severe reaction, but it can happen. So education helps, and I recommend to the patients to discuss with a medical provider the potential of those immunotherapy-related adverse events that usually, if they occur, can be managed with proper treatment to try to suppress, “cool down,” the immune system. So education is important. Dr. Gilligan: So just to summarize then, this is a trial for patients who would normally be treated with surgery alone, and we're looking at whether adding immunotherapy before and after surgery can improve those outcomes. Dr. Grivas: That's exactly right. Especially for those patients who cannot safely undergo chemotherapy before the surgery. Dr. Gilligan: And how are we going to measure whether it's successful? Whether that immunotherapy has improved outcomes or not? Dr. Grivas: The two measures that we're are looking at in this particular trial are the following. Number one, we tried to see how many patients--what is the proportion of patients from everybody who gets in the trial—who has no residual cancer cells at the time of the removal of the bladder, at the cystectomy. When the pathologist looks at the cystectomy sample in the lab after the bladder is removed from the body, what is the proportion of patients with no cancer inside the bladder after the immunotherapy compared to no immunotherapy at all? So we're going to compare these. We call this “complete response,” meaning no cancer is found in the bladder after its been removed, after the immunotherapy. And we're going to compare this complete response in the two groups. The other metric we use is to see how many patients have no recurrence regardless, meaning the cancer came back after the treatment. After the cystectomy, how many of those patients either had the cancer come back later or died from another cause. So we use these metrics and we compare the two metrics in the two populations in the trial with and without immunotherapy before the surgery. Dr. Gilligan: And currently, the relapse rate's roughly 50 percent, so we're hoping for a lower number than that. Dr. Grivas: Correct. We try to look for a lower number, and we try to see to compare these two populations with and without immunotherapy and see if immunotherapy adds value in that particular setting. Dr. Gilligan: Is this trial still open and do you know when we might see results from it? Dr. Grivas: The trial is open. It started recently, so I will strongly encourage the patients to discuss with their providers and look at particular locations where this trial is open. So definitely, there is room to go. And I think the trial will take a few years to complete and then report the results. So definitely an ongoing trial options for the patients. Dr. Gilligan: Great. Well, thank you very much. So an exciting trial for patients with localized bladder cancer going through surgery to see if we can improve outcomes, increase the cure rate, by adding this interesting new immunotherapy. Thank you, Dr. Grivas. Dr. Grivas: Thank you so much. Dr. Gilligan: So now we're going to move on and talk about the COSMIC-313 trial with Dr. Zhang from the Duke Cancer Institute. [Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313)] Can you tell us who this trial is designed for, or which group of patients? Dr. Zhang: Absolutely. We know that for patients with kidney cancer with a clear cell component and intermediate or poor risk by IMDC criteria, that both immunotherapy combinations with ipilimumab and nivolumab as well as the targeted therapy blocking blood vessel formation, called cabozantinib, have both demonstrated significant benefit for these patients. And these are approved treatments. So this particular trial is attempting to combine these starting as a triplet of ipilimumab, nivolumab, cabozantinib for four cycles and then maintenance nivolumab with cabozantinib. And this triplet treatment is compared to a placebo-controlled regimen of the same immunotherapies without the targeted therapy. Dr. Gilligan: So if a patient weren't going to go on this trial, what's the current standard of care? Dr. Zhang: Both the immunotherapy combination as well as having the cabozantinib by itself, are our standard of care therapies for these patients in these categories. Dr. Gilligan: Is this restricted to any particular group of kidney cancer patients? Dr. Zhang: These patients must have at least one of the IMDC criterion. So these are markers of inflammation, like high neutrophil count, low hemoglobin, or high platelet levels, high calcium levels, as well as poor performance status in less than one year from diagnosis to needing these type of treatments. Patients have to have kidney cancer that spread to other sites of their body or locally advanced disease which is not surgically resectable. And as a note, other treatments that are approved in patients who have intermediate poor risk disease include combinations of immunotherapies with targeted therapies like pembrolizumab with axitinib or avelumab with axitinib. Dr. Gilligan: So then just to be clear, these are drugs that are already being used, have already been shown to work, and we're trying to see if we combine them do we get a better result than using them by themselves. Dr. Zhang: That's right. And I think that's a main point. If two agents work on their own, can they be combined to work better? It is important to note that we must follow these patients for their side effects to make sure that the benefit of the triplet therapy would be worth the potential added toxicity of this combination. Dr. Gilligan: So as you mentioned, there's already a standard treatment that includes targeted therapies, immunotherapies, axitinib and pembrolizumab. What do you think is the interesting or different about the approach in this study? Dr. Zhang: The main difference of this triplet combination is the addition of ipilimumab which is a CTLA 4 inhibitor. This is even a bit of a stronger immunotherapy, which targets the dendritic cell interaction with cells to activate the immune cells even more. And so we know that ipilimumab in kidney cancer does drive increase the ability for us to achieve a complete response, meaning that this combination is a really active immunotherapy combination for metastatic kidney cancer. So if we can add the ipilimumab effect with a very strong targeted effect of the cabozantinib the thought is that this triplet might be even more effective than the current standard of care, pembrolizumab-axitinib or avelumab-axitinib combinations. Dr. Gilligan: Thank you for clarifying that. Just to make sure our listeners are clear on this. They're two doublets that are already approved—two kinds of immunotherapy or immunotherapy combined with targeted therapy. This will be the first triplet, if I understand correctly, that if this is shown to be more effective, it would be the first triplet therapy where we're using three different agents, our strongest immunotherapy combined with targeted therapy. Is that a fair summary? Dr. Zhang: Absolutely. I think that's a great summary. Dr. Gilligan: So how will success be evaluated? What are the endpoints for this? Dr. Zhang: Success for this particular study will be evaluated by improving time until tumor growth and the safety of the triplet combination so the primary outcome of this particular study is improving progression free survival. But one of the key secondary endpoints, of course, is to make sure that the benefit of this triplet is worth the potential combined side effects. And then also to follow patients and see if it also improves survival to make patients live longer. Dr. Gilligan: Do we have any sense of how long it'll be before we see outcomes from this? Or results? Dr. Zhang: This is an ongoing international trial enrolling in the US but also spanning Europe, Asia, South America, Australia, and New Zealand sites. It will enroll up to 676 patients, and it's open currently. And patients should discuss it with their oncologist and see if it's open in a site close to them. Dr. Gilligan: Dr. Grivas earlier told us about some of the side effects or risks with immunotherapy. This is combining immunotherapy with targeted therapy. Can you say a little bit about what we're gonna be watching for in terms of side effects or what we might expect? Dr. Zhang: Sure. I think all of the immunotherapy side effects that Dr. Grivas told us about pertain to this study as well. The rashes, the diarrhea, inflammation of the lungs or liver, and affected endocrine dysfunction. But the targeted therapies can also have high blood pressure, rashes on the hand and feet, so called hand foot syndrome, also diarrhea, and elevation of liver enzymes, as well as the loss of protein in the urine. I think the one overlapping toxicity of cabozantinib with a combination of ipilimumab and nivolumab, the immunotherapy combination, is the diarrhea. So patients who start on this trial should be careful to report any diarrhea early on so that their oncologist and their investigators on the study can get an early handle and manage their diarrhea well. Dr. Gilligan: Thank you. That's very helpful. One last question, I want to get back to that issue of eligibility. Sometimes when cancer patients want to go on a trial and they find that they are told they're not eligible to go on, this trial looking at intermediate risk patients specifically so a good risk patient might want to go on it and couldn't. Can you say a little bit about how those decisions are made and what the rationale for selecting groups of patients for trials is? Dr. Zhang: Sure. We know that the IMDC criteria were really made in the setting of targeted therapies, and they were a set of prognostic markers and markers of inflammation, for example, and of time from initial diagnosis to treatment. But now they've been used often as stratification markers in our treatment trials and as selection now for eligibility. In particular for this patient population, ipilimumab, nivolumab seem to have more benefit in this intermediate and poor risk population. And so that's why, for this particular study, they're selecting specifically those patients with intermediate poor-risk disease. Dr. Gilligan: So we want to focus on the patients who are most likely to benefit, it sounds like you're saying. Dr. Zhang: That's right. So the favorable risk patient population do have a better prognosis in general, but those patients may not have as much benefit from the immunotherapy doublet. Dr. Gilligan: All right. Thank you. Well, that brings us to the end of this podcast. Thanks for listening. 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. This is Timothy Gilligan. Thank you very much. ASCO: Thank you, Drs. Gilligan, Pal, Grivas, and Zhang. 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.

32: What’s on the Horizon in Metastatic Urothelial Carcinoma

CURE Talks Cancer

Play Episode Listen Later Jul 1, 2020 14:43

The treatment paradigm for metastatic urothelial carcinoma has shifted significantly over the last decade with immunotherapy and precision medicine. In this episode of the “CURE Talks Cancer” podcast, we spoke with Dr. Elizabeth Plimack, chief of the Division of Genitourinary Medical Oncology at Fox Chase Cancer Center, Temple Health, and Dr. Sumanta (Monty) Pal, from City of Hope Comprehensive Cancer Center, about metastatic urothelial. The experts discussed the treatment landscape for this disease, how patients can learn more about their options and what they have to look forward to on the horizon.

horizon metastatic carcinoma fox chase cancer center sumanta monty pal genitourinary medical oncology

Clinical Trials in Genitourinary Cancers: KEYLYNK-010, KEYNOTE-866, PDIGREE

Play Episode Listen Later May 5, 2020 27:19

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.

Clinical Trials in Genitourinary Cancers: VISION, INTACT, and PROSPER

Play Episode Listen Later Feb 13, 2020 29:04

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. Sumanta (Monty) Pal, Dr. Neeraj Agarwal, Dr. Petros Grivas, and Dr. Tian Zhang. 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 Novartis, Genentech Roche, and 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 Novartis and Bristol-Myers Squibb. 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 Genentech Roche 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 Genentech Roche and Bristol-Myers Squibb. View full disclosures for Dr. Pal, Dr. Agarwal, Dr. Grivas, and Dr. Zhang at Cancer.Net. Dr. Pal: Hi, I'm Monty Pal from City of Hope. I'm the Associate Editor for Genitourinary Cancers for Cancer.Net, ASCO's patient education website. I'm really excited to be here with my colleagues: Dr. Petros Grivas, Dr. Neeraj Agarwal, and Dr. Tian Zhang. We're really excited about this effort. We're hoping it brings some salient details about clinical trials straight to you, our most important audience. Keep in mind that clinical trials are the main way that doctors are able to find better treatments for diseases like cancer. And before any new drug can be approved by the FDA, it must be studied in the context of a clinical trial. Patient participation is vital for clinical trials. By participating in a clinical trial, you can directly help researchers develop better treatments, reduce side effects, or even reduce the risk of cancer altogether. While you may receive new treatments within a clinical trial, the primary purpose of these studies is to move the field of cancer research forward. Keeping participants safe is probably the most important concern in clinical trials, and there may be some risks involved. Because of that, your healthcare team is going to discuss with you in detail these risks before you join on to a clinical study. Now, at this point in time, we're going to discuss 3 studies that are being done in the area of kidney, bladder, and prostate cancer. These studies were chosen by members of the Cancer.Net Editorial Board Genitourinary Cancers panel from the Trials in Progress abstracts that are going to be presented at ASCO's 2020 Genitourinary Cancers Symposium. I'd like to note that none of us have any direct involvement with any of these trials. Each one of us will post our disclosures on the ASCO website if you'd like to see them. We'll certainly have them posted on the Cancer.Net website. I'd like to begin by introducing my very esteemed panel. First, is Dr. Tian Zhang, who's an expert in kidney, bladder, and prostate cancer from Duke Cancer Research Institute. We have Dr. Neeraj Agarwal, who heads up the Genitourinary Cancers Program at the Huntsman Cancer Institute at the University of Utah. And last, but not least, we have Dr. Petros Grivas from the Fred Hutchinson Cancer Research Institute in Seattle, Washington, an expert in many disease types, including bladder cancer. I'd like to bring on my first guest, Dr. Neeraj Agarwal, to discuss the VISION study. [VISION: An International, Prospective, Open Label, Multicenter, Randomized Phase 3 Study of 177Lu-PSMA-617 in the Treatment of Patients With Progressive PSMA-positive Metastatic Castration-resistant Prostate Cancer (mCRPC)] Neeraj, this is a study in prostate cancer. What particular patient population within prostate cancer are we focused on here with this study? Dr. Agarwal: So this is a patient population with advanced prostate cancer where prostate cancer has gone beyond prostate to different parts of the body. In technical terms, we call it metastatic prostate cancer. The usual treatment paradigm for these patients is to be treated with hormonal blockade therapies, which can include injections and oral pills, which have different mechanisms to prevent stimulation of testosterone to the prostate cancer cells. However, every patient with metastatic prostate cancer eventually are failed by these treatment options, and the next commonly used treatment option is chemotherapy, which usually controls the disease for a period of many months, up to one year. And after, patient's disease progresses on these 2 different therapeutic options, which include hormonal therapies and chemotherapies. And this is the patient population in which this novel type of radiation therapy or radiation particle treatment is being tested. Dr. Pal: Tell us about what question this study aims to answer. Dr. Agarwal: This study is testing a novel medication, which is a type of a radiation particle, which is supposed to target prostate cancer cells. So whether using this kind of radiation particle in patients with advanced prostate cancer, who have been failed by previous chemotherapy and novel, hormonal therapies. The study is asking whether using this radiation particle as a treatment may improve overall survival. Dr. Pal: Now, this compound is called 177Lutetium-PSMA-617. It's a long name. Tell us about what it actually does. What's the rationale for using this particular drug? Dr. Agarwal: I would like to divide this long name into 2 parts to make it simple. So 1 is the lutetium particle, which is the radiation particle, is a type of radiation known as beta radiation. So lutetium is tagged onto a PSMA-identifying agent known as PSMA-617. So if we just inject PSMA-617, it will go and seek prostate cancer cells, which are expressing PSMA on their surface. If you tag this radiation particle lutetium to the PSMA-617, what essentially happens is that PSMA-617 takes this radiation particle directly to the prostate cancer cells. Dr. Pal: Now, what is this study attempting to demonstrate? Dr. Agarwal: This study is specifically looking at 1 question, which is whether using this radiation particle can improve survival in patients with metastatic prostate cancer who have had disease progression on novel hormonal therapies and chemotherapies. Dr. Pal: And again, it's hard to be comprehensive in a podcast like this, so of course, we refer patients to their physicians for a discussion around safety of these drugs. But could you tell us about any known risks that patients should be aware of in the context of this agent? Dr. Agarwal: Yes. So as you can imagine, this PSMA-617, which is loaded with this radiation particle, is looking for those cells in our body which are expressing PSMA. So of course, the PSMA is expressed highly by prostate cancer cells. But there are also normal cells which express PSMA to a lesser degree. And those cells may also have the potential to be targeted by this radiation particle. So technically, their other cells which may express PSMA, or which are in the vicinity of these cancer cells in the bone, such as bone marrow, these can be targeted to a much lesser degree because of the specificity of this compound. We can see some off-target toxicities, as we call them, but given the highly targeted nature of this compound, those toxicities are usually very well tolerated, except in rare circumstances. Dr. Pal: Excellent, Neeraj. Now, for a little additional commentary on the VISION trial, I'm going to throw it to Dr. Tian Zhang, again, an expert at the Duke Cancer Research Institute Tian, you've had some experience enrolling patients on VISION, correct? Dr. Zhang: That's right, Monty. Thanks so much for having me on. And VISION has actually completed accrual. It was open for a few months here at Duke. We were able to enroll about 10 patients and we're really looking forward to seeing the results of VISION over the next year or 2. And I think it'll be quite applicable to clinical practice. Now, I want to mention that although VISION has completed enrollment, there are other clinical trials that are using PSMA-targeted Lutetium-617 agent as a possibility for other patients to enroll on to other trials in clinical development as we speak, and so there will be other opportunities to receive this agent. Dr. Pal: We're going to shift gears now from prostate cancer and move on to the topic of bladder cancer. And again, I'm thrilled to have Dr. Petros Grivas from the Fred Hutch Cancer Research Institute to discuss a very important trial called INTACT. [Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer (Study SWOG/NRG 1806)] Petros, the study INTACT really addresses a very important question. Can you tell us a little bit more about it? Dr. Grivas: Thank you, Monty. I think this trial is very important for a number of reasons. Number 1 is trying to address an important clinical question, which is the following: Patients who we consider candidates for bladder-preservation approach, meaning, we try to keep the bladder in place and still kill the cancer, which is not a good option for everybody with bladder cancer. But the proportion of patients after discussions of pros and cons with their providers could be offered this bladder-preservation approach, which is consisted of an optimal resection of the tumor through a procedure called transrectal bladder tumor resection, which means try to remove the bladder tumor through a procedure that is similar to cystoscopy, when you look inside the bladder. And after this tumor is removed, then there is a combination of chemotherapy and radiation, at the same time—we call this concurrent or concomitant—at the same time, chemotherapy and radiation. This approach, which involves the collaboration between the urologic oncologist, medical oncologist, and radiation oncologist, is the standard of care, the standard approach, how we try to preserve the bladder and still kill the cancer in those patients who are considered good candidates for this approach, which, as I've mentioned, is not for everybody. The clinical question is can we improve upon this backbone of chemotherapy and radiation, which is current standard of care, by using a third modality, a third type of treatment, which is immunotherapy? And immunotherapy is known to improve how people live in patients who have metastatic bladder cancer. For example, there's this particular drug called atezolizumab, which is already having FDA approval for patients with metastatic bladder cancer. The question is can we add this drug, the immunotherapy drug, that is activating the immune system, into the backbone of chemotherapy and radiation and use all three approaches, chemotherapy, radiation and immunotherapy together? And if that's the case, is that triplet combination better or not to the current standard of care, which is chemotherapy and radiation? So the INTACT trial is chemotherapy, radiation, plus immunotherapy with this drug called atezolizumab, together, all 3 of them compared to chemotherapy and radiation alone, in order to see whether we can improve upon the results we're getting with chemotherapy and radiation. The primary end point of this particular trial is what we call bladder intact disease-free survival, which means the proportion of patients who have no cancer coming back after treatment. They have what we call a complete response, remission of the cancer, and they still have the bladder intact, in place. And this is what we call a metric of success. This is a huge effort among different investigators across the country. These studies open in multiple cancer centers and sites across the nation. And I think it's a very good example of what can happen in terms of a clinical trial design that is applicable to many patients when different collaborations take place and when people put their minds together. So we're really very enthusiastic about this study, and we'll try to support the accrual and offer this option to the patients who are considered to be good candidates for this attempt for bladder preservation. Dr. Pal: Petros, thanks. That was a great overview of the study. You've really highlighted the rationale and some detail and the metrics for success of this trial. Now, on the subject of this approach, are there any risks that you think patients should be particularly aware of? And again, we leave it to the discretion of treating physicians to have that very thorough discussion of risks and benefits. But off the top of your head what would you counsel patients, in general? Dr. Grivas: I think, Monty, that's a great question, in general, because when a patient is undergoing evaluation for a clinical trial, it's important for them to understand thoroughly the pros and cons of this particular therapy and other procedures and what those mean for the patient's logistical, day-to-day schedules, as well as potential short-term and long-term side effects. In that particular study, I think the important take-home message is we're trying to evaluate the additional role of immunotherapy to the backbone of chemotherapy and radiation. So potential side effects of immunotherapy are something that are very important to be discussed with the patient. Some of the patients may develop fatigue or some degree of occurrence of what we call immune-related adverse events, which means the immune system gets activated, stimulated against the cancer but can, potentially, in a small proportion of patients generate a significant reaction, an immune system activated related reaction against different parts of the body or some parts of the body. So I think it's very important for the patients to discuss carefully with the providers what are those uncommon, but sometimes significant, immune-related adverse events, and have a very good understanding of what symptoms [to] look for in order to be able to communicate or recognize early those potential side effects and have a proper management plan. Because most of those side effects could be managed properly, and with good success, especially if they're caught up early. So I think it's important to have these thorough discussions with the provider. And of course, the side effects of chemotherapy and radiation should be discussed in thorough detail. This is the standard of care, but still is important to delineate what potential side effects can happen. At the end of the day, it's in the balanced discussion about pros and cons. This is a very exciting trial, but I think good education for the patient and their families and their caregivers are very important and critical for the successful detection or diagnosis of any potential side effects. Overall, I think this is a very relevant discussion to have with the provider and a very exciting trial to be involved in. Dr. Pal: Excellent, Petros. Well, great discussion of some of the risks associated with this approach. Neeraj, any thoughts on INTACT? Why should patients be excited about this particular trial? Dr. Agarwal: I was recently talking to one of my patients about this upcoming trial, who is preparing to go on radiation therapy plus chemotherapy as a treatment option for his muscle-invasive bladder cancer, and cystectomy is not an option. And the way I explained this to the patient is 95% of the work he will have to do will be done by the time he's getting radiation therapy and chemotherapy. And after that, 5% of the work, as far as patient's effort, side effects, toxicities, impact, and quality of life, all are concerns, 95% of that, in my view, is coming from radiation therapy and chemotherapy. And after that, little work from that perspective by the patient has to be done by atezolizumab, as far as getting treatment with atezolizumab is concerned. So as Petros said, this is a highly well-tolerated treatment, which is immunotherapy. And if you look at the potential of this drug to control the recurrence of the disease and allow our patients to maintain their bladder—it’s tremendous. So I think the expected returns are very high, and how much effort patients will have to put on the trials are not as high as you would expect if you are thinking about a trial. Dr. Pal: That was an excellent discussion of toxicities associated with this particular regimen, Neeraj. Petros, before we move on any closing thoughts? Dr. Grivas: No, I agree completely with Neeraj. I think these are important points. I just wanted to add a couple of key take-home message for the patients. Number 1, this trial is available for patients who either are or are not candidates for radical cystectomy, which is the removal of the bladder and again, it has to be a discussion with the providers whether they're good candidates for the attempt for bladder preservation. Half of the patients get the standard of care, which is chemotherapy and radiation at the same time, and the other half get chemotherapy and radiation, plus this immunotherapy called atezolizumab. And again, I think the last point to make is that chemotherapy and radiation have to happen at the cancer center, and some of the patients live far away, so I think it's important to discuss with the patients the pros and cons of the trial because it might entail some back and forth transportation for them if they have to get the radiation and the chemotherapy in the cancer center that is offering the trial. But overall, as Neeraj pointed out, we are very enthusiastic, and I'm personally enthusiastic about the study. Dr. Pal: That's great Petros, appreciate that. Now, in the final portion of our program, we're going to shift gears and talk about the type of cancer that I actually focus on personally in the clinic, and that is kidney cancer. And we have our resident expert in kidney cancer on the Cancer.Net panel, Dr. Tian Zhang from Duke here to discuss the PROSPER study, a very important national effort. [A Phase 3 Randomized Study Comparing Perioperative Nivolumab vs. Observation in Patients With Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)] Tian, can you tell us about PROSPER? Dr. Zhang: PROSPER is a phase III trial that's open currently for patients who have locally advanced kidney cancer, and we know that in this population of patients who have locally advanced kidney cancer who undergo their surgery, there's still a high rate of recurrence up to about 50% with many dying, unfortunately, from disease recurrence. And so the question that PROSPER aims to answer is can we prevent disease from recurring, and thereby, can we allow patients to live longer from giving up-front systemic therapy in addition to their surgery? And so in kidney cancer, we know that patients will benefit from immune checkpoint inhibitors, and the big question of the study is that with the primary kidney cancer in place, what is the effect of this immunotherapy called nivolumab before and after surgery compared to surgery alone, and how should we use these immunotherapy agents in the perioperative setting to improve overall survival? Dr. Pal: That's very interesting. Of course, in kidney cancer, just as we discussed with prostate cancer, you've got patients who have the disease confined to the kidney. You have patients where the disease has spread. What particular patient population does this study focus on? Dr. Zhang: This study is enrolling patients with locally advanced disease, so either clinical stage II or higher. So that's patients who have primary tumors of greater than seven centimeters, or if they have positive lymph nodes on their scan, so clinical detection of lymph node-positive cancer. Or the study, actually, also allows cancer that has spread to no more than three, so one, two, or three, other sites, which can also be definitively treated at the time of the primary surgery. Patients who have disease spread to the lung, adrenal gland, lymph nodes, pancreas, or soft tissue are allowed. Patients who have spread to the liver or bone are not allowed. And the study is currently ongoing, Monty. It is randomizing up to 805 patients total. As of late January 2020, they're currently at about 390 patients already enrolled. So there's plenty more, about 400 more patients to go on the study. And it is an open and enrolling study. Dr. Pal: That's really interesting. Now, Petros gave us some insights as to the rationale for using immunotherapy in cancer. Is it the same rationale for using this treatment strategy in kidney cancer? Dr. Zhang: Sure. So our standard of care in this setting, as you know, for locally advanced disease is truly just nephrectomy alone to remove the kidney, usually without treatment afterward. And there are multiple adjuvant studies using immunotherapies in this post-operative setting, however, those are all pending. And we're hoping that immunotherapy used earlier in the disease course will allow us to see a benefit overall. Now, nivolumab, the immunotherapy that's studied in the PROSPER trial, is approved for metastatic kidney cancer. And therefore, we know nivolumab is effective at extending overall survival for these patients. And so the question is if we can use this active immunotherapy agent earlier in the disease course if we can to try to prevent disease recurrence. Dr. Pal: That makes a lot of sense. Now, what is this particular study attempting to demonstrate? What are we trying to prove here with this trial? Dr. Zhang: Right. So the primary outcome of PROSPER is the time to disease recurrence or spread to other sites, what we call recurrence free-survival. There are secondary outcomes. So trying to get patients to live longer, overall survival, toxicity of giving nivolumab up front for these patients. As well as, specifically in patients who have clear cell kidney cancer, the time to disease recurrence for those patients, as well. So there are patients who are on the control cohort of surgery alone, and we'll be able to study that tissue in conjunction and compare those with patients who have received immunotherapy or nivolumab prior to their surgeries. So they have a number of biomarkers planned for the tissue that's being collected from the study. Dr. Pal: Very interesting. Well, I can't wait to see the results, ultimately, of this trial. But in the meantime, Petros had outline some of the risks associated with immunotherapy in the context of the study he discussed. Anything to add to that, in terms of the risks that might be entailed in this trial? Dr. Zhang: Right. So it is certainly a randomized trial, as Petros mentioned, so there are patients who are randomized to surgery alone versus patients who are randomized to the immunotherapy up front. So one dose of nivolumab followed by surgery and then maintenance treatment with nivolumab. And I fully agreed with the toxicity profile that Petros outlined very nicely. And when we get patients started on these immunotherapies treatments in clinic, I often talk about, we're activating your immune system, and therefore, toxicities can occur where the immune system is very active. So on the skin it can cause a rash, in the GI tract it can cause diarrhea or colitis, in a very small proportion of patients it can cause inflammation in the lungs or liver, and then, finally, it can affect their endocrine organs: the pituitary, thyroid, adrenal glands, and pancreas. And one more note about treatment with these immune checkpoint inhibitors of nivolumab, and other agents like nivolumab, is that these are really not for patients who have active autoimmune disease. We think that those patients who have active autoimmune disease requiring prednisone or other disease-modifying agents, those patients are probably going to have worsening of their baseline autoimmune disorder. So patients who do have that need to have a very close discussion with their providers before going on any of these trials. Dr. Pal: Well, that's an excellent overview of toxicity, and again, just as I mentioned earlier, I certainly leave it in the hands of the patient and their respective clinicians to go through a very thorough discussion of toxicity, but I think that was a fantastic primer on it, Tian. Thank you for that. Before we close, I wanted to go to Petros for any additional comments on this concept of the PROSPER study. Petros, any additional thoughts? Dr. Grivas: I think that Tian did a wonderful job summarizing all the key points. I think one of the key characteristics of this trial is, again, their rationale. The reasoning behind it, which as Tian mentioned, is we have the immunotherapy up front in the beginning of the treatment while the tumor is still present and the proteins, the antigens of the tumor, are still present, and that might be relevant in the recognition of those elements by the immune system when you give the immunotherapy. And then you have surgery, and then you have continuation of postoperative treatment, as Tian mentioned, and maybe that combination approach may be relevant. We have to see, of course, but I think it's a very, very compelling design that makes sense, at least scientifically speaking. The other point, I think, is as [inaudible] already mentioned, this very [inaudible] teamwork, team effort from multiple investigators across the country. And that speaks volumes of the very nice design, as well as the collaborative in spirit, which I think is important for that patient to know, that people do work together to come up with these clinical trials. We all hope that this trial will keep accruing well and will end up with accrual target in order to answer this important question which is, as Tian mentioned, whether immunotherapy before and after surgery prolongs life and improves the times of cancer remission, which is important and clinically relevant question. And of course, it's a key point to have discussions about sometimes uncommon but significant immune-related reaction and go through the different nuances carefully with the providers when a patient's considering clinical trial. But clinical trials, as you mentioned Monty, is the way to develop new therapies and are very important part of a discussion in the routine patient care. Dr. Pal: Excellent, Petros. Well, on behalf of Dr. Petros Grivas, Dr. Neeraj Agarwal, and Dr. Tian Zhang, I really want to thank you for joining our very first podcast from Cancer.Net. There's so many different clinical trials out there enrolling patients with genitourinary cancers, and we've only had time here to discuss 3 of them. If you have interest in participating in clinical trials, please do get in touch with your healthcare team. And of course, Cancer.Net serves as an excellent resource to communicate with experts in the field and learn more about respective genitourinary types of cancer. Thank you again for joining. ASCO: Thank you, Drs. Pal, Agarwal, Grivas, and Zhang. 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.

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Dr. Monty Pal: From an Early Commitment to Medicine Down the Path to ASCO & GU Oncology Leadership

West Wind (Audio)

Play Episode Listen Later Jun 11, 2019 32:12

Dr. Sumanta (Monty) Pal of City of Hope Comprehensive Cancer Center describes his precocious entry into medicine, the tremendous opportunities it has afforded him in ASCO leadership and GU oncology, his commitment to mentorship, & his work/life balance.

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Dr. Monty Pal: From an Early Commitment to Medicine Down the Path to ASCO & GU Oncology Leadership

West Wind (Video)

Play Episode Listen Later Jun 11, 2019 32:12

Dr. Sumanta (Monty) Pal of City of Hope Comprehensive Cancer Center describes his precocious entry into medicine, the tremendous opportunities it has afforded him in ASCO leadership and GU oncology, his commitment to mentorship, & his work/life balance.

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Who Benefits from Immunotherapy?

GRACEcast Treatments and Support Video

Play Episode Listen Later Apr 6, 2015 18:41

Immunotherapy Forum Video #27: Immunotherapies work well in some, but not in others. Who benefits, and why? Dr. Sumanta (Monty) Pal explains what doctors are learning.

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Who Benefits from Immunotherapy?

Play Episode Listen Later Apr 6, 2015 18:41

Immunotherapy Forum Video #27: Immunotherapies work well in some, but not in others. Who benefits, and why? Dr. Sumanta (Monty) Pal explains what doctors are learning.

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Who Benefits from Immunotherapy?

Play Episode Listen Later Apr 6, 2015 18:41

Immunotherapy Forum Video #27: Immunotherapies work well in some, but not in others. Who benefits, and why? Dr. Sumanta (Monty) Pal explains what doctors are learning.

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Kidney Cancer Immunotherapy Q&A

Play Episode Listen Later Mar 18, 2015 9:52

Immunotherapy Forum Video #22: Drs. Lauren Harshman and Sumanta (Monty) Pal answer questions from the audience following their presentations on immunotherapy for kidney cancer. Moderated by Dr. Marianne Davies.

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Kidney Cancer Immunotherapy Q&A

Play Episode Listen Later Mar 18, 2015 9:52

Immunotherapy Forum Video #22: Drs. Lauren Harshman and Sumanta (Monty) Pal answer questions from the audience following their presentations on immunotherapy for kidney cancer. Moderated by Dr. Marianne Davies.

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Kidney Cancer Immunotherapy Q&A

Play Episode Listen Later Mar 18, 2015 9:52

Immunotherapy Forum Video #22: Drs. Lauren Harshman and Sumanta (Monty) Pal answer questions from the audience following their presentations on immunotherapy for kidney cancer. Moderated by Dr. Marianne Davies.

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Kidney Cancer Immunotherapy: Reasons for Cautious Optimism

Play Episode Listen Later Mar 16, 2015 18:46

Immunotherapy Forum Video #21: Dr. Sumanta (Monty) Pal reviews the past, present, and future of immunotherapy for kidney cancer and expresses concern about early study results of newer treatments.

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Kidney Cancer Immunotherapy: Reasons for Cautious Optimism

Play Episode Listen Later Mar 16, 2015 18:46

Immunotherapy Forum Video #21: Dr. Sumanta (Monty) Pal reviews the past, present, and future of immunotherapy for kidney cancer and expresses concern about early study results of newer treatments.

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Kidney Cancer Immunotherapy: Reasons for Cautious Optimism

Play Episode Listen Later Mar 16, 2015 18:46

Immunotherapy Forum Video #21: Dr. Sumanta (Monty) Pal reviews the past, present, and future of immunotherapy for kidney cancer and expresses concern about early study results of newer treatments.

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Dr. Sumanta (Monty) Pal: What Are the Main Types of Kidney Cancer and Are They Managed Differently?

Play Episode Listen Later May 24, 2013 1:27

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, describes the main types of kidney cancer and discusses the differences in their management

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Dr. Sumanta (Monty) Pal: What Are the Main Types of Kidney Cancer and Are They Managed Differently?

Play Episode Listen Later May 24, 2013 1:27

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, describes the main types of kidney cancer and discusses the differences in their management

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Dr. Sumanta (Monty) Pal: What Are the Main Types of Kidney Cancer and Are They Managed Differently?

Play Episode Listen Later May 24, 2013 1:27

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, describes the main types of kidney cancer and discusses the differences in their management

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Dr. Sumanta (Monty) Pal: What Are the Options for Second Line Treatment of Kidney Cancer?

Play Episode Listen Later May 15, 2013 2:40

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to second line treatment of kidney cancer.

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Dr. Sumanta (Monty) Pal: What Are the Options for Second Line Treatment of Kidney Cancer?

Play Episode Listen Later May 15, 2013 2:40

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to second line treatment of kidney cancer.

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Dr. Sumanta (Monty) Pal: What is the Role of Surgery in the Treatment of Metastatic Kidney Cancer?

Play Episode Listen Later May 2, 2013 3:03

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, describes the role of surgery in the treatment of metastatic kidney cancer.

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Dr. Sumanta (Monty) Pal: What is the Role of Surgery in the Treatment of Metastatic Kidney Cancer?

Play Episode Listen Later May 2, 2013 3:03

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, describes the role of surgery in the treatment of metastatic kidney cancer.

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Dr. Sumanta (Monty) Pal: What is the Role of Surgery in the Treatment of Metastatic Kidney Cancer?

Play Episode Listen Later May 1, 2013 3:03

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, describes the role of surgery in the treatment of metastatic kidney cancer.

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Dr. Sumanta (Monty) Pal on the Role of Chemotherapy in the Treatment of Kidney Cancer

Play Episode Listen Later Apr 24, 2013 3:17

Dr. Sumanta (Monty) Pal reviews the current role of chemotherapy in the treatment of kidney cancer.

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Dr. Sumanta (Monty) Pal on the Role of Chemotherapy in the Treatment of Kidney Cancer

Play Episode Listen Later Apr 24, 2013 3:17

Dr. Sumanta (Monty) Pal reviews the current role of chemotherapy in the treatment of kidney cancer.

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Dr. Sumanta (Monty) Pal on the Role of Chemotherapy in the Treatment of Kidney Cancer

Play Episode Listen Later Apr 23, 2013 3:17

Dr. Sumanta (Monty) Pal reviews the current role of chemotherapy in the treatment of kidney cancer.

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What is the Right Surgery for Early Stage Kidney Cancer?, by Dr. Monty Pal

Play Episode Listen Later Mar 25, 2013 3:05

Dr. Sumanta (Monty) Pal reviews the questions on the role of surgery and what type of surgery to pursue for early stage kidney cancer.

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What is the Right Surgery for Early Stage Kidney Cancer?, by Dr. Monty Pal

Play Episode Listen Later Mar 25, 2013 3:05

Dr. Sumanta (Monty) Pal reviews the questions on the role of surgery and what type of surgery to pursue for early stage kidney cancer.

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What is the Right Surgery for Early Stage Kidney Cancer?, by Dr. Monty Pal

Play Episode Listen Later Mar 25, 2013 3:05

Dr. Sumanta (Monty) Pal reviews the questions on the role of surgery and what type of surgery to pursue for early stage kidney cancer.

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Dr. Monty Pal on Leading Options for First Line Treatment of Advanced Kidney Cancer

Play Episode Listen Later Mar 19, 2013 3:16

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to first line treatment of metastatic kidney cancer.

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Dr. Monty Pal on Leading Options for First Line Treatment of Advanced Kidney Cancer

Play Episode Listen Later Mar 19, 2013 3:16

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to first line treatment of metastatic kidney cancer.

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Dr. Monty Pal on Leading Options for First Line Treatment of Advanced Kidney Cancer

Play Episode Listen Later Mar 18, 2013 3:16

Dr. Sumanta (Monty) Pal, medical oncologist at City of Hope Cancer Center in Duarte, CA, explains the range of options and his approach to first line treatment of metastatic kidney cancer.

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Dr. Pal on the Role of Interleukin-2 (IL-2) in Advanced Kidney Cancer Today

Play Episode Listen Later Mar 11, 2013 2:21

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center discusses the current role of interleukin-2 (IL-2) in the context of many other treatment alternatives for metastatic renal cell carcinoma.

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Dr. Pal on the Role of Interleukin-2 (IL-2) in Advanced Kidney Cancer Today

Play Episode Listen Later Mar 11, 2013 2:21

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center discusses the current role of interleukin-2 (IL-2) in the context of many other treatment alternatives for metastatic renal cell carcinoma.

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Dr. Pal on the Role of Interleukin-2 (IL-2) in Advanced Kidney Cancer Today

GRACEcast Bladder Cancer Video

Play Episode Listen Later Mar 10, 2013 2:21

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center discusses the current role of interleukin-2 (IL-2) in the context of many other treatment alternatives for metastatic renal cell carcinoma.

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Dr. Monty Pal: Reviewing Bladder Cancer Stages, the Role of Surgery, and the Potential Role of Chemotherapy for Localized Bladder Cancer

Play Episode Listen Later Mar 7, 2013 3:41

Dr. Sumanta (Monty) Pal, City of Hope Cancer Center, summarizes basic stages of bladder cancer, value of surgery, and survival benefit of neoadjuvant (pre-operative) chemotherapy for higher risk muscle-invasive bladder cancer.

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Dr. Monty Pal: Reviewing Bladder Cancer Stages, the Role of Surgery, and the Potential Role of Chemotherapy for Localized Bladder Cancer

Play Episode Listen Later Mar 7, 2013 3:41

Dr. Sumanta (Monty) Pal, City of Hope Cancer Center, summarizes basic stages of bladder cancer, value of surgery, and survival benefit of neoadjuvant (pre-operative) chemotherapy for higher risk muscle-invasive bladder cancer.

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Dr. Monty Pal: Reviewing Bladder Cancer Stages, the Role of Surgery, and the Potential Role of Chemotherapy for Localized Bladder Cancer

Play Episode Listen Later Mar 7, 2013 3:41

Dr. Sumanta (Monty) Pal, City of Hope Cancer Center, summarizes basic stages of bladder cancer, value of surgery, and survival benefit of neoadjuvant (pre-operative) chemotherapy for higher risk muscle-invasive bladder cancer.

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Dr. Monty Pal on the Current Best Practices for Early Stage Kidney Cancer

Play Episode Listen Later Mar 5, 2013 2:13

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center in Duarte, CA describes optimal management of kidney cancer that is confined to the kidney, including surgery and the role of any additional post-surgical treatment.

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Dr. Monty Pal on the Current Best Practices for Early Stage Kidney Cancer

Play Episode Listen Later Mar 5, 2013 2:13

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center in Duarte, CA describes optimal management of kidney cancer that is confined to the kidney, including surgery and the role of any additional post-surgical treatment.

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Dr. Monty Pal on the Current Best Practices for Early Stage Kidney Cancer

Play Episode Listen Later Mar 5, 2013 2:13

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center in Duarte, CA describes optimal management of kidney cancer that is confined to the kidney, including surgery and the role of any additional post-surgical treatment.

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Dr. Monty Pal: How Do We Work Up a Kidney Mass That May Be Cancer?

Play Episode Listen Later Feb 27, 2013 1:55

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center in Duarte, CA reviews a recommended approach to the workup of a kidney mass suspected to be a cancer.

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Dr. Monty Pal: How Do We Work Up a Kidney Mass That May Be Cancer?

Play Episode Listen Later Feb 27, 2013 1:55

Dr. Sumanta (Monty) Pal of City of Hope Cancer Center in Duarte, CA reviews a recommended approach to the workup of a kidney mass suspected to be a cancer.

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Dr. Monty Pal: How Do We Work Up a Kidney Mass That May Be Cancer?