Podcasts about lenvatinib

Join us in this exciting episode of the Oncology Brothers podcast as we dive into the highlights from ESMO 2024, focusing on gastrointestinal malignancies. Hosts Drs. Rohit and Rahul Gosain are joined by Dr. Kristen Ciombor, a GI medical oncologist from Vanderbilt University, to discuss four key studies that have significant implications for clinical practice. In this episode, we covered: •⁠ ⁠LEAP-012 Study: An update on HCC treatment with Lenvatinib and Pembrolizumab combined with TACE, exploring the promising progression-free survival (PFS) data and the need for mature overall survival (OS) results. •⁠ ⁠Keynote-811: The current standard of care for HER2-positive gastroesophageal junction and gastric adenocarcinoma, highlighting improved OS with Pembrolizumab, chemotherapy, and Trastuzumab. •⁠ ⁠POD1UM-303 Trial: A groundbreaking study in metastatic anal cancer that shows significant OS improvement with the addition of the PD-1 inhibitor Retifanlimab to chemotherapy. •⁠ ⁠NICHE-2 Study: A remarkable update on MSI-high patients, showcasing a 100% three-year disease-free survival rate with neoadjuvant immunotherapy. Tune in for an insightful discussion that will keep you updated on the latest advancements in GI oncology! Don't forget to like, subscribe, and hit the notification bell for more conference highlights and oncology discussions. #OncologyBrothers #ESMO24 #GIMalignancies #CancerResearch #Podcast Subscribe for more updates and insights from the Oncology Brothers! Website: http://www.oncbrothers.com/ Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com  

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.12.548688v1?rss=1 Authors: Wang, S., Cheng, H., Li, M., Wu, H., Zhang, S., Gao, D., Huang, Y., Guo, K. Abstract: Although increasing studies has demonstrated that cell competition widely involved in the growth and homeostasis of multicellular organisms is closely linked to tumorigenesis and development, the mechanistic contributions to the association between tumor cell competition-driven heterogeneity and drug resistance remains ill-defined. In our study, lenvitinib-resistant hepatocellular carcinoma (HCC) cells display obviously competitive growth dominance against sensitive cells through reprogramming energy metabolism. Mechanistically, when BCL2 interacting protein3 (BNIP3) overexpression activates mitophagy activity in lenvatinib-resistant HCC cells, energy imbalance signal caused by reduced mitochondrial oxidative phosphorylation levels provokes the phosphorylation of AMP-activated protein kinase (AMPK) sensor; subsequently, enabled AMPK specifically targets enolase 2 (ENO2) to enhance glycolysis and eventually promots the competitive capacity and dominant growth. Of note, BNIP3 deficiency shows certain inhibition of cell competition outcome. Our findings emphasize a vital role for BNIP3-AMPK-ENO2 signaling in maintaining the competitive outcome of lenvitinib-resistant HCC cells via regulating energy metabolism; meanwhile this work recognaizes BNIP3 as a promising target to overcome HCC drug resistance. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

This is the last of the three-part podcast series, Keeping up with the Chemos on Lenvatinib/pembrolizumab.  Our multidisciplinary panel will discuss the challenges with patient monitoring while on Lenvatinib/pembrolizumab.  The panel discusses personal clinical experiences and lessons learned.  When to dose adjust and hold or even discontinue Lenvatinib/pembrolizumab. Once again, the session ends with take home points for patient monitoring while on Lenvatinib/pembrolizumab.  2022-2023 SGO Chemotherapy/Targeted Therapies Subcommittee Members and Moderators:Tracilyn Hall, MDJudith A. Smith, B.S., Pharm.D, BCOP, CPHQSpeakers:Jennifer MacDonald, Pharm.D, BCOPPamela Soliman, MDSound engineered and produced by Betheon Whyte on behalf of the Society of Gynecologic Oncology.

The first three-part of the Keeping up with the Chemos podcast series focused on tisotumab vedotin, and now this second installment series focuses on lenvatinib/pembrolizumab, which highlights some general information on lenvatinib/pembrolizumab including mechanism of clinical indications for prescribing. The multidisciplinary panel will discuss the aspects of getting a team of nursing, pharmacy, Gynecologist and Ophthalmologist/Optometrist educated and prepared for giving lenvatinib/pembrolizumab. The session wraps up with some key take home points on lenvatinib/pembrolizumab. 2022-2023 SGO Chemotherapy/Targeted Therapies Subcommittee Members and Moderators:Tracilyn Hall, MDJudith Smith, PharmDSpeakers:Jennifer MacDonald, PharmD, BCOPPamela Soliman, MDSound engineered and produced by Betheon Whyte on behalf of the Society of Gynecologic Oncology.

This is the second of the three-part podcast series, Keeping up with the Chemos on lenvatinib/pembrolizumab. Our multidisciplinary panel will discuss the important information about creating chemotherapy orders and instructions, any consults/monitoring by other specialties, the drug preparation and interventions during administration lenvatinib/pembrolizumab. The session ends with general take home points on administration and patient monitoring period. 2022-2023 SGO Chemotherapy/Targeted Therapies Subcommittee Members and Moderators:Tracilyn Hall, MDJudith Smith, PharmDSpeakers:Dew Hilton, Specialty Pharmacy Technician Jennifer MacDonald, PharmD, BCOPPamela Soliman, MDSound engineered and produced by Betheon Whyte on behalf of the Society of Gynecologic Oncology.

Drs Sumanta Pal and Martin Voss discuss second-line treatment of renal cell carcinoma, including current studies and agents used in the refractory setting. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968745). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Renal Cell Carcinoma Treatment & Management https://emedicine.medscape.com/article/281340-treatment Comparative Effectiveness of Axitinib Versus Sorafenib in Advanced Renal Cell Carcinoma (AXIS): A Randomised Phase 3 Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61613-9/fulltext Cabozantinib Versus Everolimus in Advanced Renal-Cell Carcinoma https://www.nejm.org/doi/full/10.1056/NEJMoa1510016 CANTATA: Primary Analysis of a Global, Randomized, Placebo (Pbo)-Controlled, Double-Blind Trial of Telaglenastat (CB-839) + Cabozantinib Versus Pbo + Cabozantinib in Advanced/Metastatic Renal Cell Carcinoma (mRCC) Patients (pts) Who Progressed on Immune Checkpoint Inhibitor (ICI) or Anti-Angiogenic Therapies. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.4501 FDA Approves Tivozanib for Relapsed or Refractory Advanced Renal Cell Carcinoma https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tivozanib-relapsed-or-refractory-advanced-renal-cell-carcinoma Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma (TIVO-3): A Phase 3, Multicentre, Randomised, Controlled, Open-Label Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30735-1/fulltext Lenvatinib, Everolimus, and the Combination in Patients With Metastatic Renal Cell Carcinoma: A Randomised, Phase 2, Open-Label, Multicentre Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/fulltext A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment (CONTACT-03) https://clinicaltrials.gov/ct2/show/NCT04338269 TiNivo: Safety and Efficacy of Tivozanib-Nivolumab Combination Therapy in Patients With Metastatic Renal Cell Carcinoma https://linkinghub.elsevier.com/retrieve/pii/S0923-7534(20)42472-X Kidney Cancer Research Summit https://kcrs.kidneycan.org/

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.

This episode is sponsored by the Osteosarcoma Institute (OSI), a nonprofit organization led by osteosarcoma experts from top U.S. cancer centers who, together, are concentrating on the cure ® for osteosarcoma. The mission of the OSI is to dramatically increase treatment options and survival rates in osteosarcoma patients through identifying and funding the most promising and breakthrough osteosarcoma clinical trials and science. In addition to advancing research, OSI also provides a free resource called OSI Connect for osteosarcoma patients. Our osteosarcoma experts can discuss available treatments, possible side effects, and provide helpful advice for getting the most out of your visits with your treating physician. This resource is available in English and Spanish and aims to help patients and families find answers to their questions. --- Dr. Nathalie Gaspar, MD, PhD, is a pediatric oncologist at Gustave Roussy Cancer Campus (Villejuif, France), head of the adolescent and young adult (AYA) unit and chair of the AYA program of the institute (SPIAJA program), since 2009. She is in charge of bone sarcomas, cancers with peak incidence in the AYA population, from biology to clinical care. Dr Gaspar is also pediatric head of the French bone adult and pediatric sarcoma group, GROUPOS. She is actively involved in early new drug development in France and in Europe, through her participation to the clinical trial committee of the Innovative Therapeutics for Child and adolescent with Cancer (ITCC) consortium and through her action as co-chair of the Fostering Age Inclusive Research (FAIR) trial initiative of the multi-stakeholder ACCELERATE platform. --- What We Do at MIB Agents: PROGRAMS: ✨ End-of-Life MISSIONS ✨ Gamer Agents ✨ Agent Writers ✨ Prayer Agents ✨ Healing Hearts - Bereaved Parent Support ✨ Ambassador Agents - Peer Support ✨ Warrior Mail ✨ Young Adult Survivorship Support Group ✨ EDUCATION for physicians, researchers and families: ✨ OsteoBites, weekly webinar & podcast with thought leaders and innovators in Osteosarcoma ✨ MIB Book: Osteosarcoma: From our Families to Yours ✨ RESEARCH: Annual MIB FACTOR Research Conference ✨ Funding $100,000 annually for OS research ✨ MIB Testing & Research Directory ✨ The Osteosarcoma Project partner with Broad Institute of MIT and Harvard ... Kids are still dying with 40+ year old treatments. Help us MakeItBetter.

Drs Sumanta Pal and Brian Rini discuss front-line treatment of renal cell carcinoma. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968736). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Bevacizumab Plus Interferon-alpha Versus Interferon-alpha Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Results of Overall Survival for CALGB 90206 https://ascopubs.org/doi/10.1200/jco.2009.27.18_suppl.lba5019 An updated table of the front-line IO combination RCC studies that have shown an OS advantage https://twitter.com/brian_rini/status/1309609380585844736/photo/1 Targeting PD-1 or PD-L1 in Metastatic Kidney Cancer: Combination Therapy in the First-Line Setting https://aacrjournals.org/clincancerres/article/26/9/2087/83102/Targeting-PD-1-or-PD-L1-in-Metastatic-Kidney Conditional Survival and Long-term Efficacy With Nivolumab Plus Ipilimumab Versus Sunitinib in Patients With Advanced Renal Cell Carcinoma https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34180 International Metastatic Renal Cell Carcinoma Database Consortium Criteria https://www.uptodate.com/contents/image?imageKey=ONC%2F116130&topicKey=ONC%2F2984&source=see_link Molecular Correlates Differentiate Response to Atezolizumab (atezo) + Bevacizumab (bev) vs Sunitinib (sun): Results From a Phase III Study (IMmotion151) in Untreated Metastatic Renal Cell Carcinoma (mRCC) https://cslide.ctimeetingtech.com/esmo2018/attendee/confcal/presentation/list?q=LBA31 Nivolumab Versus Everolimus in Patients With Advanced Renal Cell Carcinoma: Updated Results With Long-term Follow-up of the Randomized, Open-Label, Phase 3 CheckMate 025 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415096/pdf/nihms-1732721.pdf Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma https://www.nejm.org/doi/10.1056/NEJMoa2035716 The Uromigos Debate: Treatment of Favorable Risk Renal Cancer https://anchor.fm/the-uromigos/episodes/Episode-67-The-Third-Uromigos-Debate---fPD1VEGF-vs-PD1CTLA4-for-front-line-renal-cancer-emjpji Health-Related Quality-of-Life Outcomes in Patients With Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab or Everolimus Versus Sunitinib (CLEAR): A Randomised, Phase 3 Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00212-1/fulltext Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313) https://clinicaltrials.gov/ct2/show/NCT03937219 A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012) https://clinicaltrials.gov/ct2/show/NCT04736706 Twitter poll questions: What magnitude of benefit is required to adopt triplets? OS https://mobile.twitter.com/brian_rini/status/1508450496104783877 What magnitude of absolute PFS benefit vs doublets is required to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508450910506295305 What would be the most convincing endpoint to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508451622564909057 Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436590/ OPtimal Treatment by Invoking biologic Clusters in Renal Cell Carcinoma (OPTIC RCC) https://www.kcameetings.org/wp-content/uploads/2021/12/IKCSNA21_TIP8_Chen.pdf

In this podcast episode from Clinical Care Options (CCO), Heinz-Josef Klumpen, MD, PhD, and Chris Verslype, MD, PhD, discuss challenges in selecting and sequencing therapy for patients with advanced hepatocellular carcinoma. Topics include:Factors to consider before selecting frontline immunotherapyRole of TKIs in the frontlineImpact of Child-Pugh status on the efficacy of immunotherapy/VEGF inhibitor combination therapyReal-world evidence on frontline immunotherapy/VEGF combination therapyFactors to consider when selecting second-line therapy including the role of TKIs and planning for multiple lines of therapyPresenters:Heinz-Josef Klumpen, MD, PhDStaff Specialist, Medical OncologistDepartment of Medical OncologyAmsterdam UMCAmsterdam, The NetherlandsChris Verslype, MD, PhDProfessorClinical Digestive OncologyKULeuvenHead of ClinicHepatologyDigestive OncologyU.Z. LeuvenLeuven, Belgium

In this episode, Jubilee Brown, MD, and Elisabeth Diver, MD, provide expert insights on new data presented at ASCO 2022 for ovarian, endometrial, and cervical cancers regarding:Subgroup analyses from KEYNOTE-826 evaluating pembrolizumab in combination with chemotherapy with or without bevacizumab in persistent, recurrent, or metastatic cervical cancerPreliminary subgroup analyses from phase III ENGOT-EN5/GOG-3055 SIENDO trial of selinexor vs placebo maintenance in recurrent endometrial cancerUpdated analyses from phase I GARNET trial of dostarlimab in dMMR/MSI-H and pMMR/MSS advanced/recurrent endometrial cancer (cohorts A1 and A2)EndoBARR trial of atezolizumab, bevacizumab, and rucaparib in previously treated recurrent and progressive endometrial cancerPhase III ATHENA-MONO trial of first-line rucaparib vs placebo maintenance after platinum-based chemotherapy in patients with advanced ovarian cancerPresenters:Jubilee Brown, MDProfessor and Division DirectorGynecologic OncologyLevine Cancer Institute, Atrium HealthCharlotte, North CarolinaElisabeth Diver, MDClinical Assistant ProfessorDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyStanford UniversityStanford Cancer InstituteStanford University Hospital and ClinicsStanford, CaliforniaContent supported by educational grants from AstraZeneca, GlaxoSmithKline, Karyopharm Therapeutics, and Merck Sharp & Dohme Corp.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries:https://bit.ly/3ufB8Js

In this episode, David Scott Miller, MD, FACOG, FACS, and Angeles Alvarez Secord, MD, MHSc, provide expert insights on key data presented at SGO 2022 for ovarian, endometrial, and cervical cancers regarding:Results from the prospective phase III PRIME study of an individualized dose for niraparib vs placebo maintenance in newly diagnosed advanced ovarian cancerFinal OS analysis from phase III SOLO-3 evaluating olaparib vs physician's choice of single-agent nonplatinum chemotherapy in gBRCAm platinum-sensitive relapsed ovarian cancerResults from the phase III SORAYA trial of mirvetuximab soravtansine, an FRα-targeting ADC with a potent tubulin-targeting maytansinoid (DM4) delivered to tumor cells, in patients with platinum-resistant ovarian cancer who had recurrence within 6 months after last platinum dose and had 1-3 prior treatmentsResults from the randomized, double-blind, placebo-controlled phase III trial of selinexor vs placebo as maintenance in patients with stage IV endometrial cancer who had a PR/CR on ≥12 weeks of first-line taxane/carboplatinThe results from a cost-effectiveness analysis for the addition of pembrolizumab to chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancerPresenters:David Scott Miller, MD, FACOG, FACSAmy and Vernon E. Faulconer Distinguished Chair in Medical ScienceDirector and Dallas Foundation Chair in Gynecologic OncologyProfessor of Obstetrics & GynecologyUniversity of Texas Southwestern Medical CenterMedical Director of Gynecologic OncologyChair, Cancer CommitteeParkland Health & Hospital SystemDallas, Texas Angeles Alvarez Secord, MD, MHSc ProfessorDivision of Gynecologic OncologyDepartment of OB/GYNDuke Cancer InstituteDuke University Health SystemDurham, North Carolina Content supported by educational grants from AstraZeneca, GlaxoSmithKline, Karyopharm Therapeutics, and Merck Sharp & Dohme Corp.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries: https://bit.ly/38xuRBv

In this first episode of two podcasts, Dr. Amit Singal and Dr. Mark Yarchoan discuss the latest data supporting their approach to selecting treatment regimens for patients with HCC, with topics including: the current challenges in the management of HCC, recommended initial workup strategies and the evolving treatment landscape in HCC. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Amit Singal, MD, MSMark Yarchoan, MDBridget O'Brien, DNP, FNP-BC, AOCNPDr Singal: consulting fees: AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Roche.Dr Yarchoan: consulting fees: AstraZeneca, Eisai, Exelixis, Genentech; other financial or material support: Bristol-Myers Squibb, Incyte.Dr O'Brien: fees for non-CME/CE services: Amgen, Novartis.

In this second episode of two podcasts, Dr. Amit Singal and Dr. Mark Yarchoan discuss how to identify, prevent and mitigate treatment-related adverse events, and review cases with careful considerations for patient-specific factors guiding treatment selection, followed by a question-and-answer session on the management of patients with HCC. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Amit Singal, MD, MSMark Yarchoan, MDBridget O'Brien, DNP, FNP-BC, AOCNPDr Singal: consulting fees: AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Roche.Dr Yarchoan: consulting fees: AstraZeneca, Eisai, Exelixis, Genentech; other financial or material support: Bristol-Myers Squibb, Incyte.Dr O'Brien: fees for non-CME/CE services: Amgen, Novartis.

In this podcast episode from Clinical Care Options (CCO), Josep M. Llovet, MD, PhD, and Markus Peck-Radosavljevic, MD, MBA, discuss second line treatment of patients with advanced hepatocellular carcinoma. Topics include:Available agents for the management of advanced hepatocellular carcinoma in the second lineThe current role of tyrosine kinase inhibitors in second-line treatment of advanced hepatocellular carcinomaOngoing clinical trials in the second-line settingPresenters:  Josep M. Llovet, MD, PhD, FAASLDProfessor of MedicineDirector, Mount Sinai Liver Cancer ProgramDivision of Liver DiseasesMount Sinai School of MedicineNew York, New YorkProfessor of ResearchLiver Unit, IDIBAPSHospital Clinic BarcelonaBarcelona, SpainUniv. Prof. Markus Peck-Radosavljevic, MD, MBAProfessor of MedicineMedical University of ViennaVienna, AustriaDepartment Chair, Innere Medizin und GastroenterologieKlinikum Klagenfurt am WörtherseeKlagenfurt am Wörthersee, AustriaLink to full program, including accompanying downloadable slidesets:https://bit.ly/2ZL9bxq

In this podcast episode from Clinical Care Options (CCO), Josep M. Llovet, MD, PhD, and Markus Peck-Radosavljevic, MD, MBA, discuss first-line treatment of patients with advanced hepatocellular carcinoma. Topics include:Atezolizumab plus bevacizumab as the current standard of careContraindications to atezolizumab plus bevacizumabThe current role of tyrosine kinase inhibitors in first-line treatment of advanced hepatocellular carcinomaOngoing clinical trials in the first-line settingPresenters:  Josep M. Llovet, MD, PhD, FAASLDProfessor of MedicineDirector, Mount Sinai Liver Cancer ProgramDivision of Liver DiseasesMount Sinai School of MedicineNew York, NYProfessor of ResearchLiver Unit, IDIBAPSHospital Clinic BarcelonaBarcelona, SpainUniv. Prof. Markus Peck-Radosavljevic, MD, MBAProfessor of Medicine, Medical University of ViennaVienna, AustriaDepartment Chair, Innere Medizin and GastroenterologieKlinikum Klagenfurt am WörtherseeKlagenfurt am Wörthersee, AustriaLink to full program, including accompanying downloadable slidesets:https://bit.ly/2ZL9bxq

In this episode,  Nicole Concin, MD, PhD, highlights key data for endometrial and ovarian cancers presented at the ESGO 2021 annual meeting, including:Pooled data from 7 phase III clinical trials evaluating surgical outcomes as prognostic factors for patients with high-grade serous, low-grade serous, mucinous, and clear cell ovarian cancerUpdate from the phase I GARNET study in patients with advanced/recurrent mismatch repair deficient/microsatellite instability‒high or proficient/stable endometrial cancerResults from the TOTEM trial evaluating the impact of minimalist vs intensive follow-up on health-related quality of life and cost for patients with endometrial cancerPresenters:Nicole Concin, MD, PhDProfessorDepartment of Gynaecology and ObstetricsMedical University InnsbruckInnsbruck, AustriaConsultant in Gynaecological OncologyDepartment of Gynaecology and Gynaecologocial OncologyKEM Evang. Kliniken Essen-MitteEssen, GermanyContent supported by an educational grant from GlaxoSmithKline.Link to full program, including a downloadable highlights slideset and ClinicalThought commentaries:https://bit.ly/30PjPnl

In this episode, Prof. Isabelle Ray-Coquard, MD, PhD, and Bernard Doger de Spéville, MD, PhD, provide expert insights on key new data from ESMO 2021 presented for endometrial and ovarian cancers including:Data from the phase III OReO/ENGOT Ov-38 trial of olaparib rechallenge in patients with recurrent ovarian cancer previously treated with a PARP inhibitor  A subgroup analysis of KEYNOTE-775, comparing lenvatinib vs pembrolizumab vs TPC, with outcomes by tumor histology and prior lines of therapyA preplanned analysis from phase III NRG-GY004 of outcomes by HRD status for olaparib with or without cediranib vs platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancerQuality-adjusted time without symptom or toxicity from the phase III PRIMA trial of maintenance niraparib vs placebo in newly diagnosed advanced ovarian cancerPresenters:Prof. Isabelle Ray-Coquard, MD, PhDProfessor of Department of Medical OncologyClinical Science Institute of the Léon Bérard CenterLyon, FranceBernard Doger de Spéville, MD, PhDMedical OncologistSTART-Madrid, Early Phase Clinical Trials UnitHospital Fundación Jiménez DíazMadrid, SpainContent supported by an educational grant from GlaxoSmithKline.Link to full program, including a downloadable highlights slideset and ClinicalThought commentaries:https://bit.ly/3dAttwi 

In this episode, Domenica Lorusso, MD, PhD, and Alexandra Leary, MD, PhD, provide expert insights on practice changing data from IGCS 2021 presented for endometrial, ovarian, and cervical cancers regarding:A subgroup analysis from phase III KEYNOTE-775 evaluating lenvatinib plus pembrolizumab efficacy in patients with advanced endometrial cancer and dMMR statusA subgroup analysis from the phase I GARNET trial─cohorts A1 and A2─in patients with advanced endometrial cancer who had received either 1 or ≥2 prior lines of therapyData from the TOTEM trial reporting survival outcomes for patients undergoing intensive vs minimalist follow-up in following treatment for endometrial cancerAn exploratory analysis from the phase III ARIEL3 trial evaluating characteristics of patients with ovarian cancer with exceptional benefit from rucaparibA post hoc analysis from the phase III NORA trial assessing efficacy of starting PARP inhibitor maintenance following either ≤4 vs >4 cycles of platinum-based chemotherapyHighly anticipated results from the phase III EMPOWER-CERVICAL 1 trial of cemiplimab vs investigator's choice chemotherapy in women with cervical cancerPresenters:Domenica Lorusso, MD, PhDAssociate ProfessorGynecologic Oncology DepartmentClinical Research UnitFondazione Policlinico Gemelli IRCCSRome, ItalyAlexandra Leary, MD, PhDMedical Oncologist and Team Leader  Gynecology Translational Research LabDepartment of MedicineGustave Roussy Cancer CenterParis, FranceContent supported by an educational grant from GlaxoSmithKline.Link to full program, including a downloadable highlights slideset and ClinicalThought commentaries:https://bit.ly/3dAttwi

The Oncology Journal Club - Delivering Oncology News DifferentlyThe Oncology Podcast, brought to you by Oncology News Australia, is proud to present Episode 48 in our series The Oncology Journal Club.Welcome to another entertaining and informative episode. We're all about the P's this week! Procrastination, P Values and yes, peeing.Eva Segelov talks us through avoiding common P Value pitfalls and understanding statistical significance. Craig Underhill looks at Bone Resorption Inhibitors in Metastatic Castration-Resistant Prostate Cancer. And Hans Prenen talks us through a fascinating study exploring how EGFR activation limits the response of liver cancer to Lenvatinib.As ever, you'll find links to all the papers, bios and twitter handles in the notes on our website.With the usual top quality banter, papers you won't hear of anywhere else and expert analysis from our Hosts, you are in for another great episode of The Oncology Journal Club!Full bios and the list of all papers discussed are available on our website.For the latest oncology news visit www.oncologynews.com.au and for regular oncology updates for healthcare professionals, subscribe for free to get the weekly The Oncology Newsletter.The Oncology Podcast - An Australian Oncology Perspective

Listen to a soundcast of the August 10, 2021 FDA approval of Lenvima (lenvatinib) in combination with Keytruda (pembrolizumab) for first-line treatment of adult patients with advanced renal cell carcinoma

Listen to a soundcast of the July 21, 2021 FDA approval of Keytruda (pembrolizumab) in combination with Lenvima (lenvatinib) for advanced endometrial carcinoma

In this episode, David Scott Miller, MD, FACOG, FACS, and Melissa M. Hardesty, MD, MPH, provide expert perspectives on new data from ASCO 2021 presented for endometrial, ovarian, and cervical cancers regarding:Results from a pilot study of pembrolizumab monotherapy in patients with Lynch-like vs sporadic MLH1-methylated endometrial cancerUpdated analyses from the phase I GARNET trial, including data for patients with dMMR solid tumors (endometrial cancer and nonendometrial cancer cohorts)Final analyses from a study of mirvetuximab soravtansine plus bevacizumab in platinum-agnostic recurrent ovarian cancerResults from the randomized phase III BOOST trial evaluating optimal treatment duration of bevacizumab in combination with carboplatin and paclitaxel in ovarian cancerHighly anticipated results from the phase III OUTBACK trial of CRT ± adjuvant CT in women with locally advanced cervical cancerA post hoc, pooled analysis, from phase I and phase II data of bintrafusp alfa, a first-in-class bifunctional fusion protein comprising a TGF-βRII (TGF-β trap) fused to a human monoclonal antibody targeting PD-L1Results from a prospective multicenter phase II trial evaluating anlotinib plus sutimlimab in recurrent/advanced cervical cancersPresenters:David Scott Miller, MD, FACOG, FACSAmy and Vernon E. Faulconer Distinguished Chair in Medical ScienceDirector and Dallas Foundation Chair in Gynecologic OncologyProfessor of Obstetrics & GynecologyUniversity of Texas Southwestern Medical CenterMedical Director of Gynecologic OncologyChair, Cancer CommitteeParkland Health & Hospital SystemDallas, Texas  Melissa M. Hardesty, MD, MPHAffiliate Associate ProfessorOB/GYN/GYN OncologyUniversity of Alaska AnchorageGynecologic Oncologist and Managing PartnerAlaska Women's Cancer CareAnchorage, AlaskaContent supported by an educational grant from GlaxoSmithKline.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries:https://bit.ly/3dAttwi

La Dra. María Teresa Bourlon de los Ríos, oncólogo médico adscrita al Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán en la Ciudad de México, México, junto al Dr. Martín Ángel, oncólogo clínico del Instituto Alexander Fleming en Buenos Aires, Argentina, nos comentan sobre lo más destacado en tumores genitourinarios presentado en ASCO 2021, resaltando los siguientes estudios: Cáncer de próstata: VISION: Estudio fase III, internacional, prospectivo, abierto, multicéntrico, aleatorizado, de 177Lu-PSMA-617 para el tratamiento de pacientes con cáncer de próstata metastásico resistente a la castración. SWOG S1216: Estudio fase III, donde se comparó la sobrevida global en pacientes con cáncer de próstata metastásico recién diagnosticados, los cuales fueron asignados al azar a la terapia de privación de andrógenos (ADT + TAK-700 vs. ADT + bicalutamida). PEACE-1: Estudio fase III, con un diseño factorial 2x2 de acetato de abiraterona + prednisona y / o radioterapia local en hombres con cáncer de próstata sensible a la castración metastásico de novo. Cáncer de vejiga: CheckMate 274: Estudio fase III con nivolumab adyuvante frente a placebo en pacientes sometidos a cirugía radical con carcinoma urotelial con invasión muscular de alto riesgo. Cáncer renal: KEYNOTE-564: Estudio fase III, donde se compara pembrolizumab vs. placebo como terapia adyuvante post nefrectomía para pacientes con carcinoma de células renales. KEYNOTE-426: Estudio fase III, donde se muestra pembrolizumab + axitinib vs. sunitinib en monoterapia como tratamiento de primera línea del carcinoma de células renales avanzado. CheckMate 9ER: Estudio fase III, donde se compara nivolumab + cabozantinib vs. sunitinib para el carcinoma avanzado de células renales. CLEAR/KEYNOTE-581: Lenvatinib / everolimus o lenvatinib / pembrolizumab vs. sunitinib como monoterapia para el tratamiento del carcinoma avanzado de células renales.

Today we bring back our popular Journal Club with a Fellow segment. We're joined by Dr. Karine Tawagi of the Oschner Clinic in Louisiana to discuss the CLEAR trial: "Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma" as published in the New England Journal of Medicine. CLEAR: doi.org/10.1056/NEJMoa2035716 Back us on Patreon! www.patreon.com/plenarysession Check out our YouTube channel: www.youtube.com/channel/UCUibd0E2kdF9N9e-EmIbUew

In this episode, Jubilee Brown, MD, and Ursula Matulonis, MD, provide expert perspectives on new data from SGO 2021 presented for endometrial and ovarian cancer including:Results from KEYNOTE-775, a phase III trial of lenvatinib plus pembrolizumab in advanced endometrial cancerResults from the confirmatory phase III ARIEL4 evaluating rucaparib vs chemotherapy in BRCA-mutated relapsed ovarian cancer5-year follow-up from SOLO-1 trial of olaparib vs placebo in BRCA-mutated, newly diagnosed ovarian cancerLong-term follow-up results from the phase III ENGOT-OV16/NOVA trial of niraparib in patients with recurrent ovarian cancerOPAL: a phase II study evaluating dostarlimab, bevacizumab, and niraparib in platinum-resistant ovarian cancerPresenters:Jubilee Brown, MDProfessor and Director of Gynecologic OncologyLevine Cancer InstituteAtrium HealthCharlotte, North CarolinaUrsula Matulonis, MDChief, Division of Gynecologic OncologyBrock Wilson Family ChairDana-Farber Cancer InstituteProfessor of MedicineHarvard Medical SchoolBoston, MassachusettsContent supported by an educational grant from GlaxoSmithKline.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries:https://bit.ly/3dAttwi 

Discussion on lenvatinib and everolimus prior to the CLEAR trial presentation.

In this episode, Mansoor Raza Mirza, MD, and Ana Oaknin, MD, PhD, discuss the implications of recent advances in the use of immunotherapy for the treatment of patients with endometrial cancer.Presenters:Ana Oaknin, MD, PhDHead of Gynecologic Tumors UnitMedical Oncology DepartmentVall d´Hebron University HospitalBarcelona, Spain Mansoor Raza Mirza, MDChief OncologistDepartment of Oncology,Rigshopitalet – Copenhagen University HospitalCopenhagen, Denmark Content based on an online CME program supported by an educational grant from GlaxoSmithKline.Link to full program:https://bit.ly/3kpJeaG

In this episode, an expert medical oncology panel led by Elizabeth R. Plimack, MD, MS, with Brian A. Costello, MD, and Martin H. Voss, MD, discusses clinical pearls for the management of patients with metastatic renal cell carcinoma (RCC). Topics include:Treating beyond progression with immunotherapyManagement of patients with less common histologic subtypes of RCCPotential biomarkers for RCCAdverse event managementPresenters:Elizabeth R. Plimack, MD, MSChief, Division of Genitourinary Medical Oncology Director, Genitourinary Clinical Research Professor, Department of Hematology/Oncology Fox Chase Cancer Center Temple Health Philadelphia, PennsylvaniaBrian A. Costello, MDAssociate Professor of Oncology and UrologyDivision of Medical OncologyMayo ClinicRochester, MinnesotaMartin H. Voss, MDClinical Director, Genitourinary Medical Oncology ServiceMemorial Sloan Kettering Cancer CenterAssistant Professor Weill Cornell Medical CollegeNew York, New YorkContent based on an online CME program supported by educational grants from Eisai, Exelixis, and Pfizer and EMD Serono.Link to full program:https://bit.ly/32IS9gx

This week, we'll discuss the efficacy of the combination of lenvatinib and pembrolizumab for patients with advanced gastric cancer. We'll also highlight key points from the recent USPSTF draft recommendation on CT screening for lung cancer. Finally, we'll review a regulatory approval in metastatic bladder cancer and hear from the principal investigator of the confirmatory trial.Coverage of stories discussed this week on ascopost.com:Lenvatinib Plus Pembrolizumab for Advanced Gastric CancerUSPSTF Issues Draft Recommendation Statement on Screening for Lung CancerFDA Approves Maintenance Avelumab for the Treatment of Advanced Urothelial Carcinoma

The combination of pembrolizumab and lenvatinib is a promising second line option for metastatic or recurrent MSS endometrial cancer, although there can be considerable toxicity and choosing appropriate patients is key.   TRANSCRIPT This JCO Podcast provides observations and commentary on the JCO article “Lenvatinib and Pembrolizumab in Patients With Advanced Endometrial Cancer” by Makker et al. My name is Meghan Shea, and I am an Instructor of Medicine at Harvard Medical School at Beth Israel Deaconess Medical Center in Boston, Massachusetts. My oncologic specialty is gynecologic oncology. Patients with advanced endometrial carcinoma have limited options after receiving the carboplatin and paclitaxel doublet for recurrent or metastatic disease. The study that accompanies this podcast evaluates the combination pembrolizumab and lenvatinib, providing a much needed second-line option for this patient population. The approval of single-agent pembrolizumab for tumors with microsatellite instability (from here on referred to as MSI high) does not have immediate relevance for the majority of patients with advanced endometrial carcinoma who have microsatellite stable disease (from here on referred to as MSS). Makker et al. now report the results of an ongoing phase 1b/2 study of pembrolizumab, an anti-PD1 antibody, and lenvatinib, an oral tyrosine kinase inhibitor that targets the VEGF-receptor, in patients with metastatic endometrial carcinoma. Eligibility criteria included patients with an ECOG 0 to 1 who had confirmed metastatic disease with less than or equal to 2 prior lines of systemic therapy. Notably the majority were not heavily pre-treated; 52.8% of patients in the study had only one prior line of systemic treatment. Patients received lenvatinib 20 mg once daily orally continuously and pembrolizumab 200 mg intravenously every 3 weeks – with a maximum duration of 2 years for pembrolizumab. All patients had imaging at baseline and then every 6 weeks for first 24 weeks and then every 9 weeks thereafter. The primary end point was objective response rate at 24 weeks. Forty-one of the 108 patients, 38%, had a response at 24 weeks with a median follow up of 18.7 months.  As expected, the MSI high tumors had a higher response rate of 63.6%, although this was a minority of the study population, only 11 patients. Most importantly, the patients with MSS tumors had a response rate of 37.2% with a median duration of response of 21.2 months. The histology did not appear to impact the response rate – the majority of patients had endometrioid (50.9%), although the study population also contained a reasonable proportion of serous and clear cell (38%) compared to the expected frequency in the general population of advanced uterine cancers. The PD-L1 status positive or negative did not correlate with response. One might question, before accepting a complicated regimen with both oral and IV chemotherapy as a new second-line standard option, whether anyone has studied the activity of either single agent lenvatinib or single agent pembolizumab in a similar population, especially for those with MSS disease. With the caveats of cross study comparisons, it appears that neither single agent is as active as the current combination. For instance, Vergote et al reported results of a phase 2 study of lenvatinib monotherapy for advanced endometrial cancer, where the response rate was only 14.3% with median progression free survival of 5.4 months. Likewise, Ott et al studied single agent pembrolizumab in endometrial cancer with 18 of 19 patients having MSS cancer, resulting in only a 13% response rate and progression free survival of 1.8 months.              So you may be wondering, what’s the catch? The issue is the potential toxicity of this doublet regimen, with 66.9% or 83 of 108 patients, having a grade 3 or 4 treatment-related adverse event. Overall 17.7% of the patients discontinued one or both drugs. Notably, pembrolizumab was never dose reduced - only dose held or discontinued. Most strikingly, 62.9%, roughly two thirds of patients, required a dose reduction of lenvatinib. Only 11 patients (that is 8.9%) stayed on full dose 20 mg of lenvatinib for greater than 6 months. The average dose for lenvatinib was 14.4 mg daily. The toxicity profile of lenvatinib may be related to the fact that it is a multi-targeted tyrosine kinase inhibitor that targets not only vascular endothelial growth factor receptors, but also fibroblast growth factor receptors, platelet-derived growth factor receptor alpha, RET and KIT. There were 51 deaths during this study; the majority occurred during follow up due to progression of disease. However, there were 16 deaths while on study, 4 considered treatment emergent adverse events and 2 judged to be treatment related.  The four deemed treatment emergent were due to gastrointestinal perforation, intestinal obstruction, general health deterioration and metabolic encephalopathy. The two deemed treatment related were from septic shock and intracranial hemorrhage. The National Comprehensive Cancer Network (NCCN) guidelines have added the combination of pembrolizumab and lenvatinib to their list of second line therapeutic options, and it also has been approved by the Food and Drug Administration (FDA). This recognizes the fact that this combination has the highest response rate of the available drugs listed, and thus should be a strong consideration for second line therapy for patients with MSS endometrial carcinoma. However, ensuring that this treatment is appropriate for a given patient is of the utmost importance.  First the patient must be a candidate for immunotherapy – ideally not on chronic prednisone and/or have an active autoimmune disease. In contrast to prescribing single agent anti-PD-1 or anti-PD-L1, a performance status of 0 to 1 is important with this combination. The most appropriate patient should have controlled blood pressure prior to initiating drug, be able to monitor their blood pressures, take their oral chemotherapy as prescribed, and readily report any new symptoms. I avoid prescribing this drug combination if the patient has a bleeding disorder, recent clotting, uncontrolled hypertension, or is at high risk of a fistula or bowel obstruction. Lenvatinib is a renally-cleared drug, and thus patients with a reduced glomerular filtration rate (GFR) require renal dosing. This is especially relevant for patients with recurrent uterine cancer, whose kidney function is dynamic, especially in the setting of hydronephrosis. In my practice, I consider starting patients with normal renal function at 14 mg lenvatinib daily, given that the vast majority of patients on study were eventually dose-reduced. Furthermore, I might start the lenvatinib dosing even lower for patients with dynamic renal function and for those who have a baseline GFR lower than 30. Overall this study provides a promising second line option for metastatic or recurrent MSS endometrial cancer, with responders having a durable response.  Patient selection and dose adjustments are key considerations to avoiding and managing toxicity. This concludes this JCO Podcast. Thank you for listening.

Discussion of FDA's approval of lenvatinib & pembrolizumab for endometrial cancer followed by a comparison of TITAN v. ENZAMET prompted by apalutamide's latest approval.

Reviewing the REFLECT (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30207-1/fulltext) study and its take-home points on selecting an agent for advanced HCC.

Key Takeaways from the ASCO-SITC Clinical Immuno-Oncology with Dr. Steven Eric Finkelstein. Welcome to the "ASCO Daily News podcast." I'm Lauren Davis and joining me today is the "Immuno-oncology Daily News" Associate Editor, Dr. Steven Eric Finkelstein with Florida Cancer Affiliates the US Oncology Network. Dr. Finkelstein, welcome to the podcast. Thank you so much for having me. The Immuno-oncology Symposium just concluded on Sunday. How was this event compared to last year's? Well, this year's event was, again, extremely exciting. This year's event featured research and discussion surrounding themes of patient-centered rational steps to move the field of immuno-oncology towards the future. Now, as many of us know, immuno-oncology has dramatically altered the treatment landscape for many malignancies, and this progress has been extremely rapid over the last decade. As the field has progressed, researchers and clinicians are pushing it towards a better understanding of how immunotherapy can affect patients and the best and most rational combination approaches can improve responses and long-term outcomes. What presentations stood out to you? Another exciting area of research was that the combination of lenvatinib and pembro yielded promising antitumor activity and progression-free survival in patients with metastatic urothelial carcinoma. In abstract 11, a Phase Ib/II study was reported. And as we know, urothelial cancer can account for 90% of all bladder cancers. Pembro monotherapy is currently approved as a first-line therapy in patients who are ineligible to receive cisplatin or platinum-based chemotherapy. It's also approved as a second-line treatment for patients with advanced or metastatic urothelial cancer. Lenvatinib, a multikinase inhibitor, a VEGFR-1 through 3, FGFR-1 through 4, PDGFR-alpha, RET, and KIT is used as a single agent in several malignancies, including thyroid cancer and hepatocellular cancer. Dr. Vogelzang, who presented the results of the study, discussed the Phase II portion of the study, which included 20 patients with histologically confirmed metastatic urothelial carcinoma. The primary outcome in the trial was immune-related resist objective response at 24 weeks. Five patients achieved such a response for an overall response rate at 24 weeks of 25%. Dr. Vogelzang's conclusion was that lenvatinib plus pembro demonstrated promising antitumor activity with manageable adverse events. The response rate warranted further investigation and lenvatinib plus pembro combination will be studied in a Phase III trial in urothelial carcinoma. What other research were you interested in? A Phase Ia/Ib trial was launched in order to evaluate the safety of LY3321367, an anti-T cell immunoglobulin-domain and mucin-domain containing molecule 3, or TIM-3 antibody. Administered alone or in combination to LY3300054, which is an antiprogrammed death ligand, or PD-L1 antibody in patients with advanced, relapsed, or refractory solid tumors. An analysis of the trial that was presented by Harding at the meeting in Abstract 12. This focused on the safety, efficacy, pharmacokinetics, and pharmodynamic results seen with these treatment regimens. The key points are as follows-- treatment-related adverse reactions were mild, i.e. Grade two or less, in both treatment groups except for one patient with a Grade three anemia in Arm B. No dose-limiting toxicities, dose-limiting equivalent toxicities, treatment-related serious adverse events, or death was observed in either treatment arm. Approximately 68% in Arm A and 88% in Arm B of patients were positive for treatment emergent antidrug antibodies related to the LY3321367. Despite antidrug antibodies, there was no effect on pharmacokinetics noted That's great. Were there any education sessions that caught your attention? I think at the 2019 ASCO SITC Clinical Immuno-Oncology Symposium, what really struck me were the keynote addresses. On March 2, the keynote lecture from Dr. Rafi Ahmed of Emory University examined the basic scientific underpinnings of the field and focused deeply on T cell exhaustion and differentiation. In a second keynote address, Dr. Jedd Wolchok, of Memorial Sloan Kettering, took a broader look of the future of immunotherapy. And his main thesis was there was a need for a more rational approach to combination therapies. Indeed, it is apparent that the combination of therapies will be an important role for our future. That's wonderful. Were there any other takeaways that were important during the symposium? ASCO and the Society of Immunotherapy of Cancer, SITC, have really focused on developing recommendations for clinical trial reporting. Indeed, we need trial reporting that addresses the unique efficacy, toxicity, combination, and sequencing aspects of immuno-oncology treatments. As many know, ASCO and SITC had convened a working group that consisted of medical oncologists, immunologists, clinical research, biostatisticians, and representatives from industry and government to develop important recommendations, also known as Trial Reporting in Immuno-oncology, or TRIO recommendations. The recommendations based on expert consensus are important given that existing data to support evidence-based recommendations are limited. The recommendations given by TRIO are intended to improve the reporting of IO clinical trials and thus, provide more complete evidence on the relative benefits and risks of immuno-oncology. Given the rapid expansion of the number of IO clinical trials and ongoing improvements to evidence base using IO treatments and clinical care, it is apparent that these recommendations will likely need regular revision. And the annual meeting of ASCO and SITC will be an important place for TRIO recommendations to continually be updated. Thank you. Again, today, my guest has been Dr. Steven Eric Finkelstein. Thank you so much for being on our podcast today. It's been an absolute pleasure. Thank you so much. And to our listeners, thank you for tuning into the "ASCO Daily News" podcast. If you're enjoying the content, we encourage you to rate us and review us on Apple Podcast.

This week's host, Dr. Thomas Karasic, is an assistant professor at University of Pennsylvania specializing in the treatment of gastrointestinal malignancies. In this episode, Dr. Karasic discusses the recent FDA approval of lenvantinib for patients with unresectable hepatocellular carcinoma. If you enjoyed this podcast, make sure to subscribe for more weekly education content from ASCO University. We truly value your feedback and suggestions, so please take a minute to leave a review. If you are an oncology professional and interested in contributing to the ASCO University Weekly Podcast, email ascou@asco.org for more information. TRANSCRIPT [MUSIC PLAYING] Welcome to the Recent Approvals episode of the ASCO University Weekly Podcast. My name is Thomas Karasic, I'm an assistant professor at the University of Pennsylvania, specializing in the treatment of gastrointestinal malignancies. Today, we will discuss the approval of lenvatinib for the treatment of patients with un-resectable hepatocellular carcinoma. As background to our discussion today, the only FDA approved therapy prior to 2017 for hepatocellular carcinoma was sorafenib. This is based on results of the SHARP trial published in the New England Journal in 2008, which demonstrated an overall survival benefit of 10.7 months in the sorafenib arm, versus 7.9 months in the placebo arm. In the 10 years after the approval of sorafenib, a number of phase III trials attempted to establish additional drugs or combination regiments in both the first line and the second line setting for advanced hepatocellular carcinoma. But all trials failed to meet their primary endpoint, and no other treatments were approved. However, in 2017, two new drugs were approved for the second line treatment of hepatocellular carcinoma-- regorafenib, a drug similar to sorafenib, as well as the PD-1 inhibitor, nivolumab. Lenvatinib is an anti-angiogenic tyrosine kinase inhibitor that targets VEGF-1 3, FGFR 1 through 4, PDGFRA, KIT, and RET. On August 16, 2018, lenvatinib was FDA approved for the first line treatment of un-resectable hepatocellular carcinoma. Two different doses were approved-- 12 milligrams for patients with actual body weight greater than or equal to 60 kilograms, and 8 milligrams for patients with actual body weight less than 60 kilograms. The approval of lenvatinib in the first line setting was based on the results of a non-inferiority study comparing lenvatinib to sorafenib for unresectable hepatocellular carcinoma. The primary endpoint of the study was overall survival. A total of 1,492 patients were recruited, and 954 patients were randomized one-to-one between lenvatinib or sorafenib. Lenvatinib was given at a dose of 12 milligrams daily for patients of at least 60 kilograms actual body weight, or 8 milligrams for those below 60 kilograms-- while sorafenib was given at the FDA approved dose of 400 milligrams twice daily. This trial met its primary endpoint of non-inferiority for overall survival. Overall survival was 13.6 months in the lenvatinib arm, and 12.3 months in the sorafenib arm. While it met its endpoint for non-inferiority, it did not establish superiority in terms of overall survival. The hazard ratio for overall survival was 0.92. Lenvatinib did demonstrate a statistically significant increase in time to progression-- 8.9 months in the lenvatinib arm, versus 3.7 months in the sorafenib arm. It also showed a statistically significant improvement in overall response rate. Using the study endpoint of modified RECIST criteria, the objective response rate with lenvatinib was 41% versus 12% with sorafenib. Using more standard RECIST 1.1 criteria, the overall response rate of lenvatinib was 19%, versus 7% with sorafenib. Adverse events were common in both arms of the study, with 57% of those treated with lenvatinib experiencing grade 3 or greater toxicity, compared to 49% of those treated with sorafenib. Toxicities that were more common with lenvatinib included hypertension, proteinuria, hypothyroidism, weight loss, anorexia, nausea, and vomiting-- while sorafenib more commonly had hand/foot syndrome and alopecia. Toxicities, such as fatigue and diarrhea, were similar between the two arms. The approval of lenvatinib marks the first positive front line study comparing an agent to sorafenib in the first line treatment for HCC. Lenvatinib demonstrated improvements in overall response rate, as well as progression-free survival, and a modest trend towards improved overall survival, although this was not statistically significant. The toxicities of sorafenib and lenvatinib were largely comparable, although some toxicities-- such as hand/foot syndrome are more common with sorafenib-- whereas hypertension and proteinuria are more common with lenvatinib. These study results established lenvatinib as a reasonable firstline option for the treatment of HCC, and choice of sorafenib versus lenvatinib can be made based on toxicity profile, as well as the symptoms of the patient that may dictate the need for an agent with a higher response. Pending results from the CheckMate 459 study, as well as other ongoing immunotherapy front line studies, may well change the sequence of immunotherapy and anti-angiogenic therapy for HCC. But for now, lenvatinib is a reasonable front line option. Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on lenvatinib and the treatment of hepatocellular carcinoma, visit the comprehensive e-learning center at university.asco.org. [MUSIC PLAYING] 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.

Successful treatment of advanced thyroid cancer often involves a combination of therapies. Dr. Sarika Rao discusses how we determine patient care plans.   TRANSCRIPT Intro: MedStar Washington Hospital Center presents Medical Intel where our healthcare team shares health and wellness insights and gives you the inside story on advances in medicine. Host: Thanks for joining us today. We’re talking to Dr. Sarika Rao, an oncologic endocrinologist at MedStar Washington Hospital Center. Today we’re talking about how to treat advanced thyroid cancer when standard treatments fail. Dr. Rao, can tell us about the main types of thyroid cancer? Dr. Rao: Yeah, sure. So thyroid cancer is, the eleventh most common cancer out there. Just briefly, it’s more prevalent in women, but tends to be a little bit more aggressive in men. There are two main types of cells within the thyroid gland - there are follicular cells and there are C cells, c as in cat. So, follicularly-derived thyroid cancer would include papillary, follicular thyroid cancer - which there’s a subsection: Hurthle - which goes with that as well as anaplastic, that’s the most advanced and most aggressive thyroid cancer but it is follicularly derived. And then the C cells that also exist and these are neuroendocrine cells - and thyroid cancer from that specific cell is called medullary thyroid cancer. So, your follicularly derived cancers are the most common, where papillary is the most prevalent. About 80 to 85 percent of all thyroid cancers are papillary. And then your follicular and Hurthle are about 10 to 15 percent and anaplastic is less than 2 percent, so that’s very rare.  And then your medullary is about 1 to 2 percent. Host: How is thyroid cancer diagnosed and treated? Dr. Rao: Generally, the treatment is, a patient finds a nodule, either on, other imaging studies, like a CAT scan or a PET scan for some other reason and a nodule is detected, or on physical exam, the physician or the patient finds, like a lump in the throat area. And then that is followed up with ultrasound and then potentially biopsy, depending on the features of the nodule. If it is thyroid cancer really the first step is surgery. Whether that’s taking out half the gland or taking out the entire gland, as well as lymph nodes, it depends on the type of thyroid cancer and the extent of the disease and the size of the nodule - it’s a very complex process but, you know, we always discuss this with, the endocrinologist and the surgeons to make a decision, in a multidisciplinary fashion. Many times, we take out the entire gland because, oftentimes, especially with the most common type of cancer which is papillary thyroid cancer, it can be multi-focal that you may not realize is on the other half of the gland. But usually a nodule is dominant when it’s greater than one centimeter that we can see on ultrasound. We can see smaller nodules than that, as well. Sometimes the ultrasound doesn’t pick up nodules on the other side. So, if a nodule is quite big on one side, then we are more likely to take out the entire gland because there’s a likely chance that a smaller cancerous site could be on the other side. But that’s a decision that’s made between the patient, surgeon and the endocrinologist. Host: Could you describe the patient care process after surgery? Dr. Rao: Right. So then, after surgery, we get the full pathology and determine the extent of the disease and how aggressive or not the cancer is. And then we follow that up with something called radioactive iodine ablative therapy. It’s a painless test. So, the way I like to explain it to my patients is, in general, thyroid loves iodine. But it involves a low iodine diet for a couple weeks prior to getting this treatment because you are trying to prime those remnant thyroid cells from, wanting that iodine even more, even though it’s a little bit different. So, making them hungry and taking up this radioactive iodine into the gland and then that will destroy any of the remnant tissue. So, they do this low iodine diet and then, most of the time, we do a diagnostic scan to see if there’s any evidence of uptake and by uptake I mean do any of those remnant cells take up that iodine and we can see it in a diagnostic scan, which is a low dose of this radioactive iodine that we give. Because, like we said before, your cells are very hungry for this iodine. We have a risk stratification for the patient. Like, depending on how advanced their disease is. And this form of treatment, by the way, is only for papillary follicular and maybe even Hurthle cell. There are two other forms of thyroid cancer which are a little bit more aggressive where we wouldn’t use this therapy, so I just want to be clear about that. So, depending on their risk stratification - how advanced their disease is and risk of recurrence, then we proceed forward with the ablative dose, which is usually a higher dose of this radioactive iodine. And then after that there are precautions where the patient needs to make sure that they’re keeping a little bit of distance from young children, or other animals, and that’s truly just so that no one else’s thyroid becomes affected. So, they’re radioactive, sort of, but it’s only for a few days and we give them a very instructive packet as to what to do. So, after that, and this, to me, is probably the most important aspect of thyroid treatment after your surgery, is TSH suppression. Host: What is TSH suppression? Dr. Rao: So, you don’t have a thyroid gland anymore, so you need that hormonal replacement with medications like Levothyroxine, which is a generic form, or Synthroid. And there are other different brands out there. In a patient who has a benign disease who had their thyroid out, we calculate a weight-based dosing for the replacement. Someone who had thyroid cancer, we actually give a little bit more of the Levothyroxine or the T4, which is the actual thyroid hormone that you no longer have, and this is so that, you give a little bit more of the dose in an effort to suppress a hormone that’s made in the pituitary which normally stimulates thyroid cells to function, called TSH. And TSH stands for thyroid stimulating hormone, so it does exactly that. So, by giving a higher dose of the actual thyroid hormone you’re effectively suppressing the TSH made in the pituitary so you’re preventing any form of stimulation of any remnant cells that may not have been ablated from the radioactive iodine or, in a patient who didn’t receive radioactive iodine, any remnant cells from getting bigger. So that is very important afterwards, and we have criteria for what we look at and what is safe for a patient. Remnant cells may or may not carry the thyroid cancer in it, but we just want to prevent recurrence of the disease. So, if you still have thyroid tissue the risk of recurrence could be higher in certain individuals and lower in others depending on, you know, the extent of the disease and that’s a risk stratification process. So, for remnant cells that are there, we try to ablate and kill them as much as we can because surgically there’s only so much you can take out. And cells, of course, you can’t see them they’re microscopic, so there’s likely to be some remnant cells after surgery and we just want to prevent recurrence of disease. That’s the goal. Host: What are the typical outcomes after treatment? Dr. Rao: So generally thyroid cancer is, in many situations, is well-behaved. Actually, in the SEER data, the percentage of death for thyroid cancer is only about 3 percent. It’s quite low. So usually, in my practice at least, I repeat an ultrasound at the six-month mark and then again at the one-year mark. And whether a patient received radioactive iodine therapy or not, at the one-year mark I will perform a test which is called a stimulated thyroglobulin test. The thyroglobulin is like our tumor marker for thyroid cancer, and its protein that’s made by the thyroid cells. So usually, you know, in someone who responded very well to therapy the thyroglobulin would be undetectable after surgery and/or radioactive iodine ablation. And that thyroglobulin is stimulated by TSH so that’s the whole purpose of keeping the TSH low because you don’t want it to be stimulated. Except when we do this test - we want to stimulate any remnant cells or any...whether it’s cancer or not, but especially if it’s in the thyroid bed. If it’s outside of the thyroid bed, then that is obviously more concerning for cancer. Host: What do you mean by thyroid bed? Dr. Rao: So, I call it thyroid bed because the thyroid is not there anymore, so at the base of the neck. Ok, so let’s say we are monitoring this patient and at the one-year mark have our ultrasound and maybe we see evidence of disease somewhere. We do this stimulated thyroglobulin level and we do another scan - again, this is with that low iodine diet that everyone quote unquote loves - and this is in an effort, to really identify disease in that manner. So, if you do the scan and you know that there is maybe evidence of disease in the ultrasound or maybe elsewhere that you’ve detected and that scan, when you perform the scan it does not take up that iodine anymore - or after several years of watching this you see growth of the disease after several treatments with radioactive iodine, then we call that radioactive refractory disease. And what that means is that your, those thyroid cells are no longer taking up the iodine, And also, in some of those cases, the tumor marker may or may not be as accurate anymore, again, due to the mutation that’s within that cell. So, at that point, you know, you decide on where the disease is - if it’s confined to the neck, maybe you want to consider reoperation. And that’s a discussion between you and the surgeon and the patient, whether they want that. Of course, all of this is dependent on age and other comorbidities and things like that, but, just in general, that’s one option, if it’s localized disease. Two, you could think about, there’s something called alcohol ablative therapy where maybe you just have one site of disease -  that has been proven by biopsy, by the way, you know, let’s say we know this is thyroid cancer but, you know, it’s failed standard therapies - then you can use the alcohol to just focally ablate that particular nodule. Host: So, you’re essentially killing the cancer cell? Dr. Rao: You are, yeah, or that nodule where the thyroid cancer lives. And this is all localized treatment. Three, you could consider radiation therapy which we less commonly use, but it is an option. Oftentimes, if the thyroid cancer metastasizes to bone, like the spine or the ribs or something like that, which we often see with the follicular thyroid cancer, radiation therapy to those sites may be indicated because those are harder to surgically resect, unless it’s large enough. If you have multiple sites of disease, and if it’s slow-growing, you could also just consider watching the patient, especially if they’re asymptomatic. And finally, we thankfully have newer drugs - they’re called Tyrosine Kinase Inhibitors and it’s a systemic therapy. It’s a form of oral chemotherapy basically. And, these are for patients who have maybe rapidly progressive disease, those who are symptomatic or those who are asymptomatic, but their disease is in locations that, you know, may be more threatening moving forward, especially if maybe there’s invasion of the cancer into the trachea. So, this is a systemic form of therapy and we have two drugs currently approved for differentiated thyroid cancer called Sorafenib, which came out a few years ago, and Lenvatinib, which was approved in 2015, I believe, and on the market. And, generally, most of the, you know, oncologists or endocrinologists would prefer Lenvatinib at this time, if needed. But there is a very high threshold to when we use those medications. So that’s kind of a last effort. We do very close surveillance with these patients and sometimes that’s the safer option actually is to just watch it. That can be very taxing on a patient to just know that they have thyroid cancer that’s still in them or a cancer that’s still in them. But I’ve actually been very surprised with the response that I have gotten from my patients because I’m just very reassuring that, you know, we are closely watching this and, if something does happen, you know, we will address this quickly and in, you know, in a proper way. But it’s very methodical, in my mind, at least initially, as to how to approach recurrent disease. Host: Thanks for joining us today, Dr. Rao. Conclusion: Thanks for listening to Medical Intel with MedStar Washington Hospital Center. Find more podcasts from our healthcare team by visiting medstarwashington.org/podcast or subscribing in iTunes or iHeartRadio.

This week's episode is on nutritional epidemiology by JPA Ioannidis; lenvatinib for hepatocellular carcinoma; nivolumab and ipilimumab for melanoma; and #medtwitter with Dr. Avi O Glasser from OHSU.

Ezra Cohen, MD, is a board-certified oncologist and cancer researcher. He cares for patients with all types of head and neck cancers, including esophageal, thyroid and salivary gland cancers. Dr. Cohen is also an internationally recognized expert on novel cancer therapies and heads the Solid Tumor Therapeutics program at Moores Cancer Center. Much of his work has focused on squamous cell carcinomas and cancers of the thyroid, salivary gland, and HPV-related oropharyngeal cancers. As a physician-scientist, he is especially interested in developing novel therapies and understanding mechanisms of sensitivity or resistance; cancer screening; and using medication and other agents to delay or prevent cancer (chemoprevention). He was recently appointed chair of the National Cancer Institute Head and Neck Cancer Steering Committee, which oversees NCI-funded clinical research in this disease. Dr. Cohen is editor-in-chief of Oral Oncology, the most respected specialty journal in head and neck cancer. A frequent speaker at national and international meetings, he has authored more than 120 peer-reviewed papers and has been the principal investigator of multiple clinical trials of new drugs in all phases of development.  In this episode, topics include: Drug therapy for patients that fail standard therapy; including surgery and RAI Not all patients have same behavior for their cancer Some cancers are aggressive Not many thyroid cancer patients are affected by this; maybe a few thousand in the U.S., but not tens of thousands What is the treatment protocol for therapy? Lenvatinib or Sorafenib is the treatment for refectory thyroid cancer Lenvatinib tends to be more effective Sorafenib is tolerated by the patient better Other options to consider include, molecular profiling or some thyroid cancers carry mutation that is targetable, or BRAF BRAF inhibitors used with thyroid cancer patients Molecular profiling DNA sequencing Side effects include, what patient will feel and those that appear in blood tests Side effects include fatigue in 60% patients, hand or foot blisters, nausea and vomiting Side effects in blood tests include high blood pressure, increase in liver enzymes, and a reduction in blood counts VEGF receptor CT scans and ultra sounds or thyroglobulin as an indicator that thyroid cancer not responsive to traditional therapy We don’t want to make the patient feel worse; the question is when to treat the patient with drug therapy Drug treatment does no cure the disease Holidays from the drug and be rid of side effects When restarting drug, disease responds again Pediatric care Immunotherapy NOTES Ezra Cohen, MD American Thyroid Association  

Dr Larkin talks to ecancertv at ASCO 2015 about the results of a randomised phase II trial of kinase inhibitor lenvatinib used in combination with everolimus in renal cell carcinoma, which saw significant improvements in progression free survival compared with everolimus alone.

Prof Schlumberger talks to ecancertv at ASCO 2014 about the results of the phase three SELECT trial, which was a multicentre, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131 radioiodine-refractory differentiated thyroid cancer (RR-DTC).