Podcast appearances and mentions of toni choueiri

Toni Choueiri discusses this combination cohort of HIF inhibition plus VEGF-R inhibition.

Dr. John Sweetenham shares highlights from Day 3 of the 2025 ASCO Annual Meeting, including new research for the treatment of advanced renal cell carcinoma and 2 studies on novel approaches in non-small cell lung cancer. Transcript Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my takeaways on selected abstracts from Day 3 of the 2025 ASCO Annual Meeting. Today's selection features studies addressing the treatment of advanced renal cell carcinoma and 2 studies exploring novel approaches in non-small cell lung cancer. My disclosures are available in the transcript of this episode. The first abstract is number 4505. This study, led by Dr. Toni Choueiri of the Dana-Farber Cancer Institute, describes the final analysis of the CheckMate 214 trial, which compared the combination of nivolumab and ipilimumab with sunitinib for the first-line treatment of advanced renal cell carcinoma. The ipi-nivo combination is approved for the frontline treatment of intermediate and poor-risk advanced renal cell carcinoma based on the primary analysis of the CheckMate 214 trial, which demonstrated a higher response rate and longer overall survival compared with sunitinib. Today's presentation provided the final safety and efficacy results for the trial with long-term follow-up of more than 9 years.  The intent-to-treat (ITT) population in this trial comprised 550 patients randomized to nivo and ipi versus 546 who received sunitinib. The final analysis showed sustained long-term benefit for the combination therapy. Patients given nivolumab plus ipi had a 29% reduction in the risk for death compared with sunitinib. For patients with intermediate or poor-risk disease, there was a 31% reduction in the risk of death.   The probability of remaining in response through 8 years was more than doubled with nivolumab plus ipilimumab versus sunitinib in the ITT population at 48% versus 19%, and in the intermediate and poor-risk population at 50% versus 23%. The other important observation is that patients with favorable-risk disease appeared to have a 20% reduction in the risk for death at 9 years and more durable responses. This suggests a possible delayed benefit for ipi and nivo in this group since these differences were not seen in the earlier analysis.   No new safety signals emerged with longer follow-up, and the results confirm the use of ipi and nivo as a standard front-line combination therapy in this disease. Since this combination has been in widespread use for some years, the results are not surprising although the subgroup analysis suggesting benefit in favorable-risk patients is likely to inform practice in the future.   Today's second abstract is number is 8506, which was presented by Dr. Tony Mok from the Chinese University of Hong Kong, describing results from the phase 3 HERTHENA-Lung02 trial. This trial compared the antibody-drug conjugate patritumab deruxtecan with platinum-based chemotherapy in patients with EGFR-mutated advanced non-small cell lung cancer following a third-generation tyrosine kinase inhibitor (TKI).  Patritumab deruxtecan, also known as HER3-DXd, comprises a fully human anti-HER3 IgG3 monoclonal antibody conjugated to a topoisomerase 1 inhibitor payload, and showed activity in a previous phase 2 trial in patients relapsing after EGFR TKI and chemotherapy.   In this phase 3 study, this agent was compared with platinum-based chemotherapy in eligible patients with an EGFR-activating mutation who had previously received 1 or 2 EGFR TKIs, at least one of which was a third-generation drug, with relapse or progression after this therapy. Five hundred and eighty-six patients were enrolled, with progression-free survival as the primary endpoint.  The primary analysis showed a 9-month progression-free survival of 29% for the experimental arm compared with 19% for platinum-based chemotherapy, for a hazard ratio of 0.77 and a P value of 0.011. With higher progression-free survival rates at 6 months and 12 months, HER3-DXd also had a better objective response rate (35.2% versus 25.3%) compared with platinum-based chemotherapy (PBC), and HER3-DXd also extended intracranial progression-free survival compared with PBC in patients with brain metastases, with a hazard ratio of 0.75. Grade 3 or more treatment-related adverse events occurred in 73% of patients treated with HER3-DXd and 57% of patients who received PBC. HER3-DXd had a higher rate of grade or more 3 thrombocytopenia, and drug-related interstitial lung disease occurred in 5% of patients in the HER3-DXd arm.   The follow-up will need more time to mature since no overall survival data are currently available, but definitely an agent to watch with interest. Moving on to today's final abstract, 8500, was presented by Dr. Pasi Jänne from the Dana-Farber Cancer Institute, describing results from the phase 2 portion of the KRYSTAL-7 study. This study is exploring the use of a potent KRAS inhibitor, adagrasib, in combination with pembrolizumab in patients with advanced or metastatic KRASG12C- mutated non-small cell lung cancer.  Adagrasib has already received accelerated approval in the U.S. for previously treated locally advanced or metastatic NSCLC with a KRASG12C mutation. A previous report from the KRYSTAL-7 study demonstrated encouraging activity in combination with pembrolizumab in the frontline setting for this patient group who also had more than 50% expression of PD-L1. The presentation today described efficacy and safety data for this drug combination across all PD-L1 expression levels.  One hundred and forty-nine patients with a median age of 67 years were treated with the combination, 104 of whom had PD-L1 expression level results available, representing the so-called biomarker population in this trial. The overall response rate for the entire study population was 44%. In the biomarker population, the overall response rate ranged from 36% in those with less than 1% PD-L1 expression to 61% for those with more than 50% expression. For all patients, the median response duration was just over 26 months, and the median progression-free and overall survival rates were 11 and 18.3 months respectively.    For the biomarker population, the median progression-free and overall survival were highest in those patients with more than 50% PD-L1. No new safety issues emerged from this analysis; the most frequent toxicities were nausea, diarrhea, and increases in transaminases. Immune-related toxicities included pneumonitis, hypothyroidism, and hepatitis. These are important results and the results of the phase 3 portion of KRYSTAL-7, which compares first-line therapy with adagrasib plus pembro versus pembro alone in the KRASG12C mutated/PD-L1 more than 50% group, will be informative. For those patients with lower levels of PD-L1 expression, the authors suggest that the treatment escalation may be beneficial, possibly including the addition of chemotherapy.  That concludes today's report. Thanks for listening and I hope you will join me again tomorrow to hear more top takeaways from ASCO25. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts.  Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the 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.  Find out more about today's speaker:    Dr. John Sweetenham    Follow ASCO on social media:     @ASCO on Twitter    @ASCO on Bluesky    ASCO on Facebook    ASCO on LinkedIn     Disclosures:   Dr. John Sweetenham:    No relationships to disclose

Drs. David Braun and Toni Choueiri join to discuss a groundbreaking Nature study on a personalized neoantigen vaccine for adjuvant renal cell carcinoma. They explore the inspiration behind the trial, how the vaccine was developed and administered, and its safety profile. The conversation also covers patient outcomes after 3-4 years, including immune responses and disease recurrence, as well as the rapid enrollment of this innovative study and what it means for the future of kidney cancer treatment. Read the publication in Nature. https://www.nature.com/articles/s41586-024-08507-5 Check out Chadi's website for all Healthcare Unfiltered episodes and other content. www.chadinabhan.com/ Watch all Healthcare Unfiltered episodes on YouTube. www.youtube.com/channel/UCjiJPTpIJdIiukcq0UaMFsA

Welcome to another episode of the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Toni Choueiri, a leading GU medical oncologist from Dana-Farber Cancer Institute. Together, they dive into the highlights from the GU ASCO 2025 conference, covering key studies and updates in the world of genitourinary oncology. Episode Highlights: •⁠  ⁠TALAPRO-2: An in-depth discussion on the role of PARP inhibitors in prostate cancer, focusing on the study's design, findings, and the importance of germline and NGS testing. •⁠  ⁠NIAGARA Update: Insights into the new standard of care for resectable muscle-invasive bladder cancer and the promising results from the perioperative approach with Durvalumab. •⁠  ⁠CheckMate-9ER Update: A look at the combination of Cabozantinib and Nivolumab in first-line metastatic RCC, including the latest findings and implications for treatment beyond the first line. •⁠  TiNivo2: Exploring the role of Tivozanib in the treatment landscape of RCC and potential sequencing strategies. Join us for this informative discussion that aims to keep community oncologists up to date with the latest advancements in cancer care. If you find this episode helpful, please share it with your colleagues and leave us a review! YouTube: https://youtu.be/OzeHhyAdF9Q Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠ Website: https://oncbrothers.com/ Don't forget to subscribe for more insights and updates from the Oncology Brothers!

Toni Choueiri discusses the updated data from different cohorts of this novel HIF inhibitor.

Dr Toni Choueiri, Chief of GU Oncology at Dana-barber Cancer Institute (Boston, USA) returns to GU Cast with members of his team at Dana Farber Cancer Institute to discuss our favourite lists of top GU Oncology papers for 2024. Toni has posted these now legendary lists at the end of each year on Twitter/X since the start of Covid, and they have become essential reading for anyone wanting a superb overview of top trials. Each tweet contains a top line summary of each trial and key images such as K-M curves, plus links to the original papers. A huge amount of work and a great resource. Today we are joined by Toni along with Dr Marc Eid and Dr Emre Yekeduz who helped compile this year's lists. We hear about the process behind it all, and we run through their Top 10 Bladder and Renal Cancer papers, and their Top 5 Prostate Cancer papers. The team also post their Top 10 Translational papers and Their Top 10 non-GU Oncology papers. Well done again to Toni, Marc, Emre and team! Links to the tweets below. Even better on our YouTube channelLinks:Top 10 Bladder and Renal Cancer Papers Top 5 Prostate Cancer Papers 

John Warner, 57, renal cell carcinoma (kidney cancer), Boston and Vero Beach, FL, with Toni Choueiri, MD, Director Lank Center for Genitourinary Oncology, Dana-Farber.

Dr. Neeraj Agarwal and Dr. Rana McKay discuss promising studies in GU cancers featured at the 2024 ASCO Annual Meeting that highlighted improved outcomes in urothelial carcinoma, improved survival in renal cell carcinoma, and the role of ctDNA as a potential biomarker for predicting outcomes.   TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah's Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News.  I am delighted to welcome Dr. Rana McKay, a GU medical oncologist and associate professor at the University of California San Diego. Today, we'll be discussing some key GU abstracts featured at the 2024 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode. Rana, we're thrilled to have you on the podcast today to share your insights on key advances in GU oncology from ASCO24. Dr. Rana McKay: Thank you so much, Neeraj; it's a pleasure to be here. Dr. Neeraj Agarwal: So, Rana, let's start with some bladder cancer abstracts. Could you tell us about Abstract 4503, titled “Impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer”? Dr. Rana McKay: Of course, I would be delighted to. First, I would like to remind our listeners that enfortumab vedotin (EV) was approved as a monotherapy for the treatment of locally advanced or metastatic urothelial cancer based on the results of EV-201 and EV-301 trials. In these pivotal studies, EV was initiated at a dose of 1.25 mg/kg, and dose modifications, such as reductions and interruptions, were used to manage adverse events. In the abstract presented at ASCO 2024, Dr. Daniel Petrylak and colleagues conducted a post-hoc exploratory analysis to evaluate the association between EV plasma exposure and outcomes. They used multiple pharmacokinetic samples collected during the first two cycles and pre-dose samples from 3 EV monotherapy studies, namely EV-101, EV-201, and EV-301, that were conducted in patients with previously treated locally advanced or metastatic urothelial carcinoma. Dose reductions to 1 mg/kg were required in 42.1% and 35.1% of patients in the EV-201 and EV-301 trials, respectively, and reductions to 0.75 mg/kg were required in 13.6% and 11.1% in the EV-201 and EV-301 trials, respectively. Higher EV exposure during the first two cycles was associated with a higher objective response rate. The ORR was 21.4% for the dose of 0.75 mg/kg, while it was 18.5% for the dose of 1.0 mg/kg. Interestingly, increasing the dosage to 1.25 mg/kg improved the ORR, which ranged from 40 to 51.1% across various studies. In the EV-301 trial, when comparing the efficacy of EV to chemotherapy, EV improved PFS and OS across all dose quartiles, and there was no evidence that recommended dose modifications impacted long-term efficacy outcomes. Dr. Neeraj Agarwal: Thank you, Rana, for this great summary. I would like to add that the meticulously conducted pharmacokinetic studies demonstrated that serum levels of EV correlated with responses. Importantly, patients who had to decrease the dose did not experience compromised outcomes as EV improved PFS and OS outcomes vs chemotherapy in across all exposure quartiles in the EV-301 trial where EV was compared with chemotherapy. These findings highlight the need to start at the recommended dose of 1.25 mg/kg and reduce it, if necessary, however, clinicians should not start at a lower dose.  Dr. Rana McKay: I totally agree with you, Neeraj. Now, moving on to a different setting in bladder cancer, what can you tell us about LBA4517, titled “Perioperative sacituzumab govitecan alone or in combination with pembrolizumab for patients with muscle-invasive urothelial bladder cancer: SURE-01/02 interim results”? Dr. Neeraj Agarwal: Of course! So, SURE was a multicohort, open-label, phase 2 study in patients with muscle-invasive bladder cancer assessing sacituzumab govitecan as a neoadjuvant therapy either alone in SURE-01 or as a combination with pembrolizumab followed by adjuvant pembro in SURE-02 in a flexible design allowing a bladder-sparing approach. In the abstract presented at ASCO 2024, Dr. Antonio Cigliola and colleagues report interim results of the SURE-01 study. Patients with cT2-4N0M0 urothelial carcinoma who were ineligible for or refused cisplatin-based neoadjuvant chemotherapy were planned to receive 4 cycles of neoadjuvant sacituzumab govitecan at a dose of 10 mg/kg followed by radical cystectomy.  An extensive assessment was performed at baseline and after the 4 cycles for response assessment. Patients with clinical complete response defined with negative MRI, cystoscopy and ctDNA assays refusing radical cystectomy were offered redo transurethral resection of the bladder tumor or repeat TURBT followed by observation in the absence of viable high-grade tumor in the bladder. The primary endpoint was pathological complete response rate, while secondary endpoints included pathological downstaging rate and safety. After the first 8 patients were enrolled, the protocol was amended due to the occurrence of grade 3 and 4 neutropenia and diarrhea in 75% and 50% of patients, respectively, and 2 deaths – one of which was deemed to be treatment-related due to sepsis. Key protocol changes included the reduction of the dose of sacituzumab govitecan to 7.5 mg/kg, the introduction of G-CSF as primary prophylaxis, and the exclusion of patients at high risk of febrile neutropenia per ASCO guidelines.  Among 21 patients who received at least one cycle of sacituzumab govitecan and included in the intention-to-treat population, 47.6% had a complete pathological response, and 52.4% had pathological downstaging. 11 patients underwent radical cystectomy, while 7 received repeat-TURBT due to complete clinical response or patient preference. Regarding the safety profile, grade 3 or more adverse events occurred in 42.5% of patients. Treatment-related adverse events leading to dose interruptions or discontinuations were more common before the protocol amendment. It is noteworthy that 3 patients died after treatment discontinuation, with one deemed treatment-related, as previously mentioned. Dr. Rana McKay: Thank you, Neeraj, for a great summary. The pathological complete responses observed show promising activity for sacituzumab govitecan as a neo-adjuvant therapy and a window for bladder-sparing approaches, which is definitely exciting news for our patients! However, although the 3 deaths encountered in a neo-adjuvant setting could be concerning, the improvement of the safety profile after protocol amendments is reassuring and supports the continuation of the study. Dr. Neeraj Agarwal: Before wrapping up the bladder cancer section, would you like to share your insights with our listeners on Abstract 4518, titled “Quantitative circulating tumor DNA (ctDNA) assessment in patients with advanced urothelial carcinoma treated with pembrolizumab or platinum-based chemotherapy from the phase 3 KEYNOTE-361 trial”?  Dr. Rana McKay: Sure. So, the KEYNOTE-361 trial was a randomized phase 3 study with 3 arms that included pembrolizumab plus chemotherapy, pembrolizumab monotherapy, or chemotherapy alone in patients with previously untreated advanced urothelial carcinoma. The results showed that neither the combination of pembrolizumab plus chemotherapy nor pembrolizumab monotherapy improved survival outcomes compared to the chemotherapy arm. So, in this exploratory analysis presented at ASCO24, Dr. Tom Powles and colleagues sought to assess the role of ctDNA as a potential biomarker between the pembrolizumab monotherapy arm and the chemotherapy arm. Tumor tissue mutations were evaluated using whole exome sequencing, and plasma ctDNA was assessed with the Guardant 360 assay. Changes in ctDNA from pre-treatment cycle 1 to on-treatment cycle 2, so 3 weeks post-baseline assessment, were quantified by the maximum variant allele frequency of tumor tissue-specific mutations.  Results showed that lower baseline ctDNA levels were associated with improved clinical outcomes of response in the pembrolizumab arm but not in the chemotherapy arm. This improvement in the pembrolizumab arm was also robust to adjustment for tumor mutational burden and PD-L1. Additionally, chemotherapy led to a ctDNA clearance rate of 41% compared to 11% in the pembrolizumab arm. Patients who had a large ctDNA reduction with pembrolizumab had significantly improved outcomes compared to those achieving a large reduction with chemotherapy with a hazard ratio of 0.25. However, this did not replicate in patients who did not achieve a large reduction, as these patients had similar outcomes across both arms. Let's switch gears to kidney cancer and start with Abstract 4508, reporting the final OS analysis from the JAVELIN Renal-101 trial. Neeraj, what would you like to tell us about this abstract? Dr. Neeraj Agarwal:  Well, as a quick reminder, the JAVELIN Renal-101 was a randomized phase 3 trial where patients with previously untreated advanced or metastatic clear cell renal cell carcinoma were randomized to receive either the combination of avelumab plus axitinib or sunitinib. In previous analyses, the combination of avelumab and axitinib significantly improved PFS compared to sunitinib and was subsequently approved by the FDA for the first-line treatment of patients with advanced RCC in 2019. This superiority in PFS was maintained across the different analyses; however, OS data remained immature. In the abstract presented at ASCO24 by Dr. Robert Motzer from Memorial Sloan Kettering Cancer Center and colleagues, the authors reported OS results at a median follow-up of around 73 months and a minimum of 68 months for all patients, which is the longest follow-up for any ICI-TKI combination in RCC. The final analysis in the overall population favored the combination of avelumab plus axitinib with a median OS of 44.8 months compared to 38.9 months with sunitinib, however, this did not reach statistical significance with a hazard ratio of 0.88. The PFS results and safety profile were consistent with previous analyses.  Dr. Rana McKay: Thank you, Neeraj, for such a nice overview of this abstract. These new data could make this regimen less optimal than other ICI-TKI combinations in the first-line mRCC setting.   Dr. Neeraj Agarwal: I concur, Rana. Moving on to perhaps one of the most exciting GU abstracts featured, Abstract 4506, titled “Circulating kidney injury molecule-1 biomarker analysis in IMmotion010: A randomized phase 3 study of adjuvant atezolizumab vs placebo in patients with renal cell carcinoma at increased risk of recurrence after resection.” Rana, what are your thoughts on this abstract? Dr. Rana McKay: Well, first, I would like to take a step back and remind our audience that in the IMmotion010 trial, patients with resected intermediate to high-risk RCC with clear cell and/or sarcomatoid component were randomized in a 1:1 ratio to receive either atezolizumab or placebo. Investigator-assessed disease-free survival, which was the primary endpoint, favored the atezolizumab arm but did not reach statistical significance. In the abstract featured at ASCO24, Dr. Laurence Albiges and colleagues build on data previously reported in the ASSURE and CheckMate 914 trials and report provocative findings regarding a molecule known as kidney injury molecule 1 or KIM-1, which is a type 1 membrane glycoprotein that has been identified as a minimally invasive potential peripheral blood circulating biomarker. The KIM-1 level of 86 pg/ml was identified as the optimized threshold for defining post-nephrectomy KIM-1 high vs KIM-1 low subgroups in the IMmotion010 trial. KIM-1 levels were measured at baseline or pre-treatment, at cycle 4 day 1, and at disease recurrence or discontinuation without disease recurrence. Baseline characteristics were balanced between the KIM-1 high and KIM-1 low groups, except perhaps for a slightly higher pathological stage in the KIM-1 high subgroup.  I would like to highlight 3 key takeaways from this abstract. First, KIM-1 high level was associated with significantly worse DFS with a hazard ratio of 1.75. Second, patients in the KIM-1 high subgroup receiving atezolizumab had a 28% reduction in the risk of recurrence or death compared to those receiving placebo, while those in the KIM-1 low subgroup had comparable outcomes across both treatment arms. Third, patients in the KIM-1 high subgroup receiving atezolizumab were significantly less likely to experience an on-treatment increase in KIM-1 levels, which was associated with worse DFS in both high and low KIM-1 subgroups, regardless of treatment arm. Thus, these findings support the use of KIM-1 as both a predictive and prognostic biomarker in patients with RCC. Dr. Neeraj Agarwal: Yes, Rana, this is amazing data! I would like to add that these results warrant larger and, ideally, prospective studies to validate the utility of KIM-1 as a noninvasive biomarker for identifying minimal residual disease after nephrectomy and for predicting outcomes to immune checkpoint inhibitors. Dr. Rana McKay: Also, in the field of biomarkers, 2 abstracts interrogating different biomarkers in a different setting, so in patients with advanced or metastatic RCC were presented. Neeraj, could you tell us more about these abstracts? Dr. Neeraj Agarwal: Of course! I think you are referring to Abstracts 4504 and 4505. In abstract 4504, Dr. Toni Choueiri and colleagues sought to assess the clinical implications of different biomarkers in the CLEAR trial, which was a randomized phase 3 trial that led to the approval of the combination of pembrolizumab plus lenvatinib in the first-line mRCC setting. On the other hand, in abstract 4505, Dr. Brian Rini presented biomarker results in KEYNOTE-426, which was also a randomized phase 3 trial based on which the combination of pembrolizumab plus axitinib was approved in patients with mRCC. The authors in both trials sought to investigate the role of biomarkers in predicting treatment outcomes from 3 different angles. Starting with PD-L1 expression, the superiority of the combination arms over sunitinib was not impacted by PD-L1 status in both trials. Moving on to RCC driver gene mutations on whole exome sequencing, such as VHL, SETD2, PBRM1, and BAP1, ICI combination therapies improved outcomes regardless of mutation gene status, and this improvement was statistically significant with PBRM1 mutations in KEYNOTE-426 compared to wild-type PBRM1, but this did not replicate in the CLEAR trial. Finally, using transcriptomic signatures derived from RCC trials, especially the IMmotion 151 and JAVELIN Renal 101 trials, where 7 clusters or molecular subtypes were identified, the combination arms outperformed sunitinib in all clusters in both trials and the magnitude of this benefit differed across clusters.  Dr. Rana McKay: Thank you for this very interesting summary and comparison of the results of these 2 abstracts. These findings support the use of ICI-based combinations in all patients with mRCC as a first-line option. Although these abstracts could not identify specific biomarkers that could guide us clinicians in treatment selection, they provide very interesting biological insights on these molecular biomarkers that are, however, not yet clinically actionable. Dr. Neeraj Agarwal: Very interesting point, Rana. Moving on to prostate cancer, let's start with abstract LBA5000 titled, “Cabazitaxel with abiraterone versus abiraterone alone randomized trial for extensive disease following docetaxel: The CHAARTED2 trial of the ECOG-ACRIN Cancer Research Group (EA8153).” Rana, what is your takeaway on this abstract? Dr. Rana McKay: As a reminder to our audience, the CHAARTED2 trial was a randomized open-label phase 2 study that compared the combination of cabazitaxel and abiraterone to abiraterone alone in patients with mCRPC previously treated with ADT plus docetaxel in the hormone-sensitive setting. The primary endpoint was progression-free survival. After a median follow-up of 47.3 months, Dr. Christos Kyriakopoulos and colleagues reported in LBA5000 that patients receiving the combination of cabazitaxel plus abiraterone had a 27% reduction in the risk of progression or death. However, there was no significant difference in overall survival between the two arms, with a median OS of 25 months in the cabazitaxel+abiraterone arm and 26.9 months in the abiraterone arm, although the study was underpowered for this endpoint. Regarding the toxicity profile, the combination of cabazitaxel and abiraterone was overall well tolerated with more cytopenias, as expected.  Dr. Neeraj Agarwal: Very nice summary of this abstract, Rana. I would like to add that the treatment landscape of patients with mHSPC has evolved since the design of the study and now includes combination therapies of ADT + ARPI with or without docetaxel, and ADT + docetaxel is no longer a standard of care, which limits the applicability of these results in clinical practice today.  Dr. Rana McKay: Excellent point, Neeraj. Let's discuss Abstract 5001, titled “CYCLONE 2: A phase 3 study of abemaciclib with abiraterone in patients with metastatic castration-resistant prostate cancer”. Dr. Neeraj Agarwal: Sure! In the abstract featured at ASCO24, Dr. Matthew Smith and colleagues report the primary results of the CYCLONE 2 trial, which was a randomized phase 2/3 study that investigated the combination of abemaciclib plus abiraterone versus abiraterone monotherapy in patients with mCRPC. Stratification factors included radiographic progression at study entry, presence of measurable disease, and prior docetaxel for mHSPC. Part 1 of the study established the recommended phase 2 dose of abemaciclib at 200 mg twice daily. In part 2, patients were randomized to placebo or abemaciclib, and an adaptive interim analysis using prespecified criteria was performed and recommended the expansion of the study to part 3. The primary endpoint was investigator-assessed radiographic progression-free survival by RECIST 1.1 and PCWG3 criteria in the intention-to-treat population. At the time of the primary analysis, adding abemaciclib to abiraterone did not improve rPFS, with a hazard ratio of 0.83. The median rPFS was 22 months for the combination arm and 20.3 months for the abiraterone arm. The combination was well tolerated, and the safety profile was consistent with the known adverse events. Dr. Rana McKay: So, the addition of abemaciclib to abiraterone did not improve outcomes in patients with mCRPC. These findings suggest that no further investigation is warranted for abemaciclib or CDK4/6 inhibitors in biomarker-unselected patients with prostate cancer.  Dr. Neeraj Agarwal: Rana, what's your take-home message on Abstract 5006, titled “Health-related quality of life results from PRESTO (AFT-19), a phase 3 randomized trial of intensification of androgen blockade in patients with high-risk biochemically relapsed castration sensitive prostate cancer”? Dr. Rana McKay: So, as a reminder to our audience, the PRESTO trial was a randomized phase 3 study that assessed the effects of intensified androgen receptor blockade in patients with biochemically recurrent prostate cancer following local therapies. Patients with a PSA doubling time of less than 9 months and no evidence of metastatic disease were randomized to receive either 52 weeks of ADT alone, ADT plus apalutamide, or ADT plus apalutamide plus abiraterone. In their paper published earlier this year in the Journal of Clinical Oncology, the authors showed that patients receiving ADT plus apalutamide with or without abiraterone had significantly longer PSA-progression-free survival than those receiving ADT alone. In the oral presentation featured at ASCO24, Dr. Ronald Chen and colleagues report health-related quality of life outcomes that were assessed using various questionnaires or scales at baseline, at cycle 7, which is around 6 months on treatment, and at the end of treatment. Results showed that this intensified approach with apalutamide did not significantly increase severe adverse events, did not lengthen the time to testosterone recovery, and did not meaningfully increase common treatment-related symptoms such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue. Importantly, additional intensification with abiraterone did not further improve PSA-PFS but did increase the rate of serious adverse events, lengthened the time to testosterone recovery, and increased hot flash interference.  Dr. Neeraj Agarwal: So, in conclusion, the PRESTO trial supports using intensified androgen blockade with apalutamide to improve PSA-PFS in patients with high-risk biochemically recurrent prostate cancer without compromising health-related quality of life. However, adding abiraterone did not offer additional benefits and increased side effects.  Dr. Rana McKay: Let's move on to LBA5002 titled, “A randomized, double-blind, placebo-controlled trial of metformin in reducing progression among men on expectant management for low-risk prostate cancer: The MAST (Metformin Active Surveillance Trial) study.” Would you like to share your insights on this abstract with our listeners? Dr. Neeraj Agarwal: Absolutely. MAST was a randomized, double-blinded, placebo-controlled trial that investigated the impact of metformin on the progression of low-risk localized prostate cancer in patients choosing to undergo active surveillance. Eligible patients had biopsy-proven, low-risk, localized prostate cancer diagnosed within the past 6 months, characterized by a Gleason score of less than 6 observed in less than one-third of the total cores, less than 50% positivity in any one core, a PSA level of less than 10 ng/ml, and a clinical-stage between T1c and T2a. Patients were randomized in a 1:1 ratio to receive either metformin 850 mg twice daily or placebo for three years. All patients underwent repeat prostate biopsy at 18 and 36 months. The primary endpoint was time to progression, defined as the earliest occurrence of primary prostate cancer therapy, such as prostatectomy, radiation, hormonal therapy, or pathological progression on subsequent biopsies, which was defined as more than 1/3 of total cores involved, at least 50% of any one core involved, or Gleason pattern 4 or higher. The study included 407 patients, with 204 receiving metformin and 203 receiving a placebo. Results presented by Dr. Anthony Joshua showed no statistically significant difference in progression-free survival, including therapeutic and pathologic progression, with an unadjusted hazard ratio of 1.08.  Interestingly, there was a signal that patients with a BMI more than 30 had a detriment to taking metformin with a higher risk of progression compared to those receiving placebo with an unadjusted HR of 2.39 and a p-value of 0.01. Dr. Rana McKay: I would like to add that this study showed that metformin use does not prevent the progression of low-risk localized prostate cancer on active surveillance and could represent a potential detriment for patients with high BMI at study entry. Dr. Neeraj Agarwal: Yes, Rana, I concur. Any final remarks before we conclude today's podcast? Dr. Rana McKay:  Thank you, Neeraj; it's been wonderful being here with you today and you having me on the podcast to highlight these important advances and the amazing work that many investigators are conducting and the patients who were involved in the context of these trials. It's really excellent to see these updated results.   Dr. Neeraj Agarwal: Before we wrap up this podcast, I would like to say that we have reviewed a selection of abstracts addressing prostate, bladder, and kidney cancer, which are significantly impacting our medical practices now and in the near future. Rana, thank you for sharing your insights today. These updates are undoubtedly exciting for the entire GU oncology community, and we greatly appreciate your valuable contribution to the discussion. Many thanks. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Find out more about today's speakers:    Dr. Neeraj Agarwal   @neerajaiims   Dr. Rana McKay  @DrRanaMcKay     Follow ASCO on social media:      @ASCO on Twitter      ASCO on Facebook      ASCO on LinkedIn         Disclosures:        Dr. Neeraj Agarwal:         Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences     Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas      Dr. Rana McKay:   Consulting or Advisory Role: Janssen, Novartis, Tempus, Exelxis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Bayer, Sanofi, Merck, Vividion, Calithera, AstraZeneca, Myovant, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Pfizer, Bayer, Tempus

Welcome to another insightful episode of the Oncology Brothers podcast! In this episode, hosts Drs. Rahul and Rohit Gosain are joined by Dr. Toni Choueiri, a GU Medical Oncologist from Dana-Farber Cancer Institute, to discuss key abstracts from ASCO 2024. They delve into topics such as the impact of the EV302 study on metastatic bladder cancer, the potential role of ctDNA as a biomarker in bladder cancer, real-world data on metastatic RCC, and the PSMA-4 study in prostate cancer. The discussion covers patient-reported outcomes, treatment strategies, and the evolving landscape of oncology care. Tune in to gain valuable insights into the latest advancements in oncology and how they are shaping the standard of care for patients. Don't miss out on this engaging conversation with experts in the field. Subscribe to the Oncology Brothers podcast for more updates from the world of oncology. Website: http://www.oncbrothers.com/ Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

Toni Choueiri and Brian describe similarities and differences in the biomarker findings of these two trials. Debate about the value and future of this approach breaks out.

For Urologists, there are not that many papers that come along where we can say - "this will almost immediately change my practice". But KEYNOTE-564 looks like one of those! A large phase III randomised trial of adjuvant pembro following nephrectomy for renal cell carcinoma in patients deemed at higher risk for recurrence. Regular listeners/viewers might remember we discussed this on GU Cast back in August 2021 when the disease-free survival endpoint was published in NEJM, and it would be fair to say we were cautious and kept saying "we need to wait for the overall survival data". Well here we are! Patients who received pembro for one year had a 38% reduced risk of death. Big news! We are joined again by Dr Alex Kutikov, Urologist at Fox Chase Cancer Centre, who joined us on the original podcast. We are also joined by his colleague GU Medical Oncologist, Dr Matt Zibelman, who has a lot of experience in this area having been an investigator on the IMmotion 010 study. Unfortunately lead author Dr Toni Choueiri could not join us this time but he gets plenty of mentions!This is a Themed Podcast supported by our Silver Partners, MSD, manufacturers of pembrolizomab, through an educational grant. MSD had no input into the content of this podcast. Even better on our YouTube channelLinks:Full NEJM paper Previous GU Cast on K-564

Renu caught up with lots of experts and friends at ASCO GU in San Francisco recently and brings you all the highlights. Hear from Toni Choueiri, Matt Cooperberg (on that debate on renaming low-grade prostate cancer), Todd Morgan, Neha Vapiwala, Morgan Roupret, Sophia Kamran, Morgan Roupret, Sam Washington, plus a great chat with Tyler Seibert while they were out for an early morning run around beautiful San Francisco. Even better on our YouTube channelGU Cast Conference Highlights are supported by our Gold Partner, Bayer China. 

Drs. Neeraj Agarwal and Todd Morgan discuss CONTACT-02, KEYNOTE-564, CheckMate-67T, and other notable studies featured at the 2024 ASCO Genitourinary Cancers Symposium, as well as additional key abstracts in prostate, kidney, and bladder cancers that will significantly influence clinical practice. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program and professor of medicine at the Huntsman Cancer Institute at the University of Utah, and editor-in-chief of ASCO Daily News. Today, we'll be discussing practice-changing abstracts and other key advances in GU oncology featured at the 2024 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Todd Morgan, the chair of this year's ASCO GU. Dr. Morgan is a urologic surgeon, chief of urologic oncology at Michigan Medicine, and a professor of urology at the University of Michigan. Our full disclosures are available in the transcript of this episode, and the disclosures of all guests on the podcast can be found at asco.org/DNpod. Todd, thank you for joining us today. Dr. Todd Morgan: Thanks so much, Neeraj. It's an honor to be here and I'm just thrilled to be able to do this with you. Dr. Neeraj Agarwal: Thank you. So, the GU meeting showcased significant advancements across the spectrum of GU malignancies. Can you tell us about the hot topics that captured the headlines this year? What did you find exciting this year at the ASCO GU Symposium? Dr. Todd Morgan: The theme of this year's meeting was "20 Years of Advancing Science and Transforming Patient Care," and this reflected ASCO GU's incredible milestone in GU cancer research over the last 2 decades. We were thrilled to welcome over 5,200 attendees from over 70 countries, and, believe it or not, there were more than 875 abstract submissions, compared to more than 300 in the meeting's first year. Most of the participants were present in person and that was fantastic. It enabled great networking opportunities and opportunities for experts, trainees, and mentees to exchange knowledge and ideas. Without a doubt, ASCO GU remains the annual meeting in our field, and it's amazing to hear the breadth and depth of the state-of-the-art science that's presented at this meeting, and so much of it impacts patient care the second that you return home. Additionally, the meeting's focus on diversity and interactivity, networking, multidisciplinary collaboration, and evidence-based care were absolutely phenomenal from my standpoint. We had a lunch session for women's networking that was a huge success—the first time we've done that. The keynote lecture by Dr. Cheryl Lee that talked about ensuring adequate representation in clinical trials was a huge hit, and we had tremendous positive feedback from that lecture. There were also multiple featured sessions on different diagnostic and therapeutic challenges in localized, recurrent, and advanced GU cancers. And, Neeraj, my personal favorite during the symposium is always the Trainee and Early-Career Networking Luncheon on the first day and then the additional networking luncheons on the 2 following days. I had great conversations with a ton of trainees and junior faculty, and I feel so fortunate for the opportunity to get to know the future superstars in our field. So I'd like to kick it back to you for a second because the first day started with a focus on prostate cancer and some of the key clinical trials. A great example is Abstract 17, which was the second oral presentation delivered, and really congratulations to you, Neeraj, on sharing the exciting data from the CONTACT-02 trial which we were eagerly awaiting. And I'd love to get your thoughts on the data that you presented. Could you tell us more about that trial? Dr. Neeraj Agarwal: Yes, Todd, I agree with you. It was such an exciting conference overall, and thank you for your leadership of this conference. So let's talk about the CONTACT-02 trial. It was a phase 3 randomized trial assessing the combination of cabozantinib and atezolizumab versus a second NHT in patients with metastatic castration-resistant prostate cancer after progression on one NHT. This patient population had to have extrapelvic soft tissue metastases, which could be liver metastases, lung metastases, or lymph nodal metastases, and about up to a quarter of patients had liver metastases. And overall, this was a high-risk patient population which was randomized to, as I said, cabozantinib plus atezolizumab versus a second line NHT. And these patients had received a prior NHT, mostly in the mCRPC setting.  The co- or dual primary endpoints were overall survival and progression-free survival (PFS). And a unique thing was that PFS was assessed only by RECIST 1.1 because, as per our discussions with regulatory authorities, the trial was focused on soft tissue metastases because of questions in the past that cabozantinib can affect bone lesions in an artifactual fashion, possibly concerns. That's why the PCWG 3 criteria were not used as the primary endpoint, but, of course, indeed used as another key endpoint, so we have information on both. Anyway, coming back to the endpoint 1:1 randomization. The randomization was stratified by presence or absence of liver metastases, prior docetaxel chemotherapy, and the setting in which NHT was given (mCSPC or CRPC). The PFS or primary endpoint was significantly improved with a 35% reduction in risk of progression or death with the cabozantinib-atezolizumab combination versus second NHT. And there was a trend for overall survival, with a hazard ratio of 0.79 favoring the cabozantinib-atezolizumab combination. Interestingly, all subgroups benefitted, regardless of age, region, site of metastases, but we decided to choose three clinical subgroups of interest such as patients with liver metastases, patients with prior docetaxel chemotherapy in the castration-sensitive setting, and bone metastases, and all these subgroups seemed to be benefitting with the strongest signal in the liver metastasis subgroup, with a 57% reduction in risk of progression or death, which I would argue we have never seen with any combination or any regimen in the metastatic prostate cancer setting yet, barring some targeted therapies in very selected patients. But overall, across the non-biomarker-selected patients, we have never seen this kind of signal. Toxicity — no discussion is complete without discussing toxicity, so I would like to highlight that. Safety signal — there were no new safety signals. The most common grade 3-4 adverse events were hypertension in 7%, anemia in 6%, which were similar in both arms, and, of course, diarrhea and fatigue in 4% each. And if we look at the secondary endpoints, such as time to chemotherapy and time to symptomatic skeletal events, they tended to favor the cabozantinib-atezolizumab. To sum it up, cabozantinib-atezolizumab showed a significant PFS benefit, with a 35% reduction in risk of progression or death, with a trend for overall survival in this patient population with an unmet need. So thank you so much, Todd, for allowing me to summarize the results of this trial. Dr. Todd Morgan: Yeah, wow. That's so impressive, and not surprising that you could so fluidly go right through all that data. Amazing. We heard some discussion of the NHT control arm in this trial. Could you discuss that for a bit? Because it obviously has implications on the similar control arm of other ongoing trials in this setting. Dr. Neeraj Agarwal: Absolutely. Pretty much all trials, every trial which has recently been reported or started in metastatic castrate-resistant prostate cancer have a similar second NHT arm. Whether there were multiple immunotherapy trials which we have just reported, or new trials which are starting or just started enrolling patients. And the reason for that is no randomized trial has ever shown superiority of docetaxel chemotherapy over a second NHT after failure of prior NHT in the mCRPC setting. That's number one. If you look at NHT as a control, it is accepted by health authorities globally with multiple recent trials which are just starting also having NHDR and it would not have been possible without the approval of global regulatory authorities across the world.  Then, if you look at the recently reported trial in the mCRPC setting with prior treatment with an NHT, there is an indication that chemotherapy may not be superior to NHT. For example, in the KEYNOTE-641 trial in patients with mCRPC with prior NHT, randomizing patients to enzalutamide plus pembrolizumab versus enzalutamide, the median PFS with enzalutamide was 9 months. This is very similar with docetaxel in patients randomized to docetaxel plus pembrolizumab versus docetaxel; the median PFS with docetaxel is 8 months or 8.3 months. And lastly, if you really want to have a comparison of chemotherapy with NHT which has been done after progression on NHT and docetaxel chemotherapy, so later line of mCRPC setting, that is the CARD trial, as you can imagine, cabazitaxel versus NHT, especially in patients with visceral metastasis, which was the point of discussion. For example, people may not feel comfortable randomizing patients to NHT compared to taxane. The hazard ratio for PFS supporting cabazitaxel was 0.79, so almost a 0.80 PFS hazard ratio, which we have never seen turning out to be a clinically significant benefit. So, if you combine all these data together, I think it was absolutely acceptable to us as investigators to have a second NHT as the control arm. And of course, when we are consenting the patient, we have to keep alternatives in mind, and we do talk about those alternatives with the patients. And if alternatives seem more applicable, we should not be talking to patients about those clinical trials or a given clinical trial in the clinic. I'm glad you brought this up, Todd, because this control NHT arm is not an issue with this trial, but all trials which should be presented in GU ASCO in the future meetings in the coming years. So, thank you. Dr. Todd Morgan: Yeah, thank you. It's such an important topic and controversy at some level, but it's a difficult problem to think about and obviously highly relevant to all the trials that we're looking at. Congrats again on that trial, that's tremendous. There was another important randomized phase 3 trial and it covers radiotherapy in patients with high-risk localized prostate cancer. Can you give us your insights on that one? Dr. Neeraj Agarwal: Yeah, Todd, I think you are referring to LBA259, titled "Long-term Results of Dose Escalation of Radiation Therapy from 70 Gy to 80 Gy Combined with Long-term Androgen Deprivation Therapy in High-risk Prostate Cancer: The GETUG-AFU 18 Randomized Trial." As you mentioned, in this randomized phase 3 trial, Dr. Christophe Hennequin and colleagues randomized patients with high-risk prostate cancer, which means they had to have either clinical stage T3 or T4 disease, or PSA ≥20 nanograms per milliliter, or a Gleason score between 8 and 10. These patients were randomized to receive ADT for 3 years combined with either dose-escalated intensity-modulated radiotherapy. So, I'd like to highlight, this was in the context of IMRT in the dose of 80 Gy or a conventional dose of 70 Gy. Now, you can argue that more people are using more than 70 Gy nowadays, but across the world, the conventional dose is still considered 70 Gy. So, 80 Gy versus 70 Gy were tested. Patients also had to have negative lymph node status on CT scans and MRI. The primary endpoint was biochemical progression-free survival or clinical progression-free survival at 5 years following the ASTRO Phoenix definition. Secondary endpoints – and these are quite important secondary endpoints – include overall survival, acute and late toxicity, and quality of life. The best part is that this trial met its primary endpoint with a 44% reduction in risk of biochemical or clinical progression or death in the dose-escalation radiotherapy arm compared with the conventional radiotherapy arm. Interestingly, a significant 52% improvement in prostate cancer-specific survival and a 39% improvement in overall survival was observed in the dose-escalated arm. So, 80 Gy continued to be superior to 70 Gy IMRT across the primary and secondary endpoints. Now, the best part is, regarding the toxicity profile, there was no significant difference between the 2 arms, with 78% of patients in the higher dose arm and 76% of patients in the conventional arm experiencing grade 2 or more toxicities. Dr. Todd Morgan: Great summary and really important, great news for our patients. Of course, it's a slightly different setting as it's high-risk localized prostate cancer. I checked in with our radiation oncologists at the University of Michigan after that [presentation] because I couldn't remember exactly where we are in terms of dose on these patients. And they were like, “Yeah, we've been doing 80 to 90 Gy for several years,” so it's great having this data to support that. And I think, as you said, the field at many centers has already moved that way. And again, the key takeaway from this abstract would be that IMRT, in combination with long-term androgen deprivation therapy, is effective and safe and increases not only the biochemical or clinical PFS rate, but also the cancer-specific survival and overall survival, again, in high-risk localized prostate cancer patients. And it does not appear to increase long-term toxicity. So really important. It'd be great to switch gears and discuss kidney cancer, if that's okay, and talk about some key abstracts in that field. What do you think? Dr. Neeraj Agarwal: There were so many exciting data in all cancers, which is amazing. So, Todd, could tell us about the LBA359, which I thought was one of the most impactful abstract presentations in the ASCO GU this year. It was titled, “Overall Survival Results from the Phase 3 KEYNOTE-564 Study of Adjuvant Pembrolizumab Versus Placebo for Treatment of Clear Cell Renal Cell Carcinoma (ccRCC)."   Dr. Todd Morgan: Yeah, this was a really big moment in our field, complete with a mid-presentation round of applause that was well deserved. And so this abstract was presented by Dr. Toni Choueiri from Dana-Farber Cancer Institute, and it included patients with clear cell renal cell carcinoma at intermediate high or high risk of recurrence, meaning that they had positive nodal disease or negative nodal disease with PT 2 and grade 4, or sarcomatoid features, or stage PT 3 or 4. These patients underwent nephrectomy with or without metastasectomy less than 12 weeks before randomization and had not received prior systemic therapy for clear cell RCC. Patients were randomized to receive either pembrolizumab 200 milligrams or placebo IV every three weeks for at least 17 cycles, or until disease recurrence, intolerable toxicity, or withdrawal of consent. Disease-free survival by investigator assessment was the primary endpoint, and overall survival was a key secondary endpoint. In this abstract, Dr. Choueiri and colleagues report results of the third prespecified interim analysis with a median follow-up of around 57 months in 496 patients receiving pembrolizumab and 498 patients receiving placebo. So, just as a reminder to the audience here, the first interim analysis reported at a median follow-up of 24 months and showed a significant reduction of 32% in the risk to recurrence or death in patients in the pembrolizumab arm. Then subsequently in November of 2021, the FDA approved pembrolizumab for the adjuvant treatment of patients with RCC who are at intermediate high or high risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions. At that time, though, overall survival data were still immature. So, at the third prespecified interim analysis with a median follow-up of around 57 months, pembrolizumab showed, for the first time in an adjuvant RCC setting, improved overall survival with a 38% reduction in the risk of death. The estimated OS rate at 48 months was 91.2% with pembrolizumab and 86% with placebo. Furthermore, the OS benefit was observed across key subgroups, including patients with non-metastatic disease, patients with metastatic but no evidence of disease, patients with PDL-1 combined positive score less than or greater than or equal to one, and patients with presence or absence of sarcomatoid features. In each of these subgroups, the forest plot looks really impressive. And the DFS benefit was similar to previously reported interim analyses with a hazard ratio of 0.72. Also, no new safety signals with pembrolizumab were observed so just tremendous data. Dr. Neeraj Agarwal: Thank you, Todd, for such a great summary of these very important results. So the key message from this abstract, as you said, is that after a median follow-up of around 57 months, which is a long follow-up, adjuvant pembrolizumab demonstrates a statistically significant and clinically meaningful improvement in overall survival versus placebo in patients with RCC at high risk of disease recurrence after surgery. And this is, by the way, the first phase 3 study to show improved overall survival with any adjuvant therapy in RCC. Basically, this means we should continue to use adjuvant pembrolizumab or at least bring it up in our discussion with our patients who are in a similar situation with high-risk RCC after surgery. So this is great news overall. Todd, there was another kidney cancer abstract, LBA360, which compared, interestingly, subcutaneous nivolumab with intravenous nivolumab in patients with metastatic renal cell carcinoma. Could you please give us your insight about this abstract?   Dr. Todd Morgan: Sure. Really interesting study. Really interesting data that were presented. So as you mentioned, CheckMate 67T was a multicenter, randomized, open-label phase three study led by Dr. Saby George and colleagues that evaluated pharmacokinetics and objective response rate non-inferiority of subcutaneous nivolumab versus IV nivolumab in patients with locally advanced or metastatic clear cell RCC. So patients with measurable disease that progressed during or after 1 to 2 prior systemic regimens and who did not receive a prior immuno-oncology treatment were randomized 1-1 to receive either subcutaneous nivolumab 1200 milligrams every 4 weeks or IV nivolumab 3 milligrams per kilogram every two weeks until disease progression, unacceptable toxicity, withdrawal of consent, completion of two years of treatment, or death. The coprimary pharmacokinetics endpoints for non-inferiority testing were time-average serum concentration over the first 28 days and minimum serum concentration at steady state determined by a population pharmacokinetics analysis. A key secondary endpoint was objective response rate by independent review. So in 248 patients receiving subcutaneous nivolumab and 247 patients receiving IV nivolumab, non-inferiority for the coprimary pharmacokinetics and key-powered secondary objective response rate endpoints were met. The relative risk ratio for objective response rate was 1.33. The median PFS by independent review was 7.23 months in the subcutaneous group and 5.65 months in the IV group. Treatment-related serious adverse events occurred in 6.5% of patients in each group, and study drug toxicity led to 3 deaths in the subcutaneous group and 1 death in the IV group. These results could support using subcutaneous nivolumab as a new option to improve healthcare efficiency, especially since the average injection time with subcutaneous nivolumab was less than 5 minutes. I think we all know what issues are going on in infusion beds across the country, including, I'm sure, your center and mine. Dr. Neeraj Agarwal: Yes, absolutely. I think this is great news for our patients, Todd. Thank you. This shows that we are not only improving therapeutic options and diagnostic tools, but maybe we're also on the right track towards more practical administration routes, assisting in addressing the treatment burden and improving the efficiencies of healthcare systems. We love to have this option available for our patients, especially those who are pressed for time. So, Todd, would you like to move on to bladder cancer now?  Dr. Todd Morgan: Yeah, Neeraj, that'll be fantastic. I'm sure listeners would love to hear more about LBA530. Could you tell us more about this one, Neeraj? Dr. Neeraj Agarwal: Of course. I think this abstract is titled "Enfortumab Vedotin in Combination with Pembrolizumab Versus Chemotherapy in Previously Untreated, Locally Advanced or Metastatic Urothelial Carcinoma: Subgroup Analysis Results from EV-302," which was a global phase three study and was presented by Dr. Michiel Van Der Heijden. As our audience may recall, the EV-302 trial was presented at the ESMO 2023 meeting by Dr Tom Powles and the results were very exciting where, for the first time, a combination outperformed traditional gemcitabine-cisplatin chemotherapy. In this trial, patients with previously untreated with metastatic advanced urothelial carcinoma were randomized 1-1 to receive a 3-week cycle of a combination of enfortumab vedotin, which, as we know, is an antibody-drug conjugate targeting nectin-4 expressed on the cancer cells and pembrolizumab, which is a PD-1 inhibitor, versus gemcitabine and cisplatin or carboplatin, which were, until recently, the standard of care in this setting, and continue to be so in many countries in the world. The combination of enfortumab and pembrolizumab reduced the risk of progression or death by 55% and reduced the risk of death by 53% in the overall population. So consistent decrease in the hazard ratios for PFS and OS, and consistent improvement in overall survival and PFS in that previously reported presentation in the ESMO 2023. Now, based on these results, this combination was recently approved by the FDA in December 2023 for patients with advanced or metastatic urothelial carcinoma. So now the abstract, which was presented at the ASCO GU 2024 meeting, reported the results of a prespecified subgroup analysis. Select secondary endpoints included objective responses, duration of response, and safety. In 442 patients receiving the combination of enfortumab vedotin plus pembrolizumab, and a similar number of patients receiving chemotherapy both PFS and OS were higher for the combination of EV and pembro among prespecified subgroups such as race, platinum eligibility, PDL-1 expression, metastatic site, involvement of the liver or kidney function. Interestingly, the combination of EV and pembro reduced the risk of death by 53% in patients with visceral metastasis and 54% in patients with node-only metastasis. The improvement in PFS seems to be consistent regardless of the site of metastasis. In patients with moderate to severe renal function, the risk of death was reduced by 50% in patients receiving combination therapy. This is one of the best findings of these results because we always face challenges in treating patients with suboptimal kidney function and we cannot use cisplatin. Overall, EV plus pembro continues to show superior efficacy compared to platinum-based regimens across subgroups across the subgroups across the site of metastasis regardless of kidney function and so on. Dr. Todd Morgan: Yeah, just amazing data. I love hearing you spell it out like that. So, thank you again for the opportunity for me to sit here with you and listen to you talk about these data. It's impressive that we have been able to expand our therapeutic arsenal for urothelial carcinoma with an immune-targeting regimen that can spare our patients potential side effects of chemotherapy. What would your final takeaway on this abstract be? Dr. Neeraj Agarwal: I agree with you, Todd. I would add that the OS benefit was consistently observed across these select prespecified subgroups, including those historically associated with poor prognosis. The results of this new analysis support the finding of primary results, which indicate that EV plus pembro is a potentially new standard of care for patients with newly diagnosed, locally advanced, or metastatic urothelial carcinoma. Before we wrap up the bladder cancer session and the podcast, Todd, could you please give us insights about LBA531? Dr. Todd Morgan: Yeah, absolutely. I loved getting to hear this abstract presented. This one is titled “Ambassador,” known as the AMBASSADOR trial aligns A031501, a phase 3 randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma versus observation, that was presented by Dr. Andrea Apolo. It's an open-label, randomized, phase 3 trial that included patients with muscle-invasive urothelial carcinoma of the bladder, upper tract, or urethra. Eligible patients had pathologic tumor stage T2 or greater and/or positive pathologic nodal disease or positive margins at surgery following neoadjuvant chemotherapy, or patients with pathologic tumor stage T3 or greater and/or positive pathologic nodal disease or positive margins at surgery without prior neoadjuvant chemotherapy, and who were cisplatin ineligible or declined adjuvant cisplatin-based therapy. These patients were randomized one to one to either receive pembrolizumab 200 milligrams every 3 weeks for 1 year or observation. The dual primary endpoints were disease-free survival and overall survival. Secondary objectives included evaluation of DFS and OS in PDL-1 positive and negative patients and assessing safety. A total of 354 patients were enrolled to receive pembrolizumab and 348 to the observation arm, and 21% of the patients in the observation arm received a subsequent immune checkpoint inhibitor. At a median follow-up of 22.3 months for DFS, the median disease-free survival in the pembrolizumab arm was 29 months, while it was only 14 months in the observation arm with a hazard ratio of 0.69. At the interim analysis, OS data showed only a trend toward better outcomes in the pembrolizumab arm, which did not, however, reach statistical significance, with a median of 50.9 months in the pembrolizumab arm and 55.8 months in the observation arm with a hazard ratio of 0.98. These results could nevertheless have been impacted by the subsequent treatment of patients in the observation arm with an immune checkpoint inhibitor, especially after the FDA approval of nivolumab in 2021 for patients with muscle-invasive urothelial carcinoma, based on results of the CheckMate 274 trial. In terms of the safety profile, grade three or more adverse events occurred in 48.4% of patients in the pembrolizumab arm and 31.8% of patients in the observation arm. Dr. Neeraj Agarwal: That's great, Todd. This is such a great summary of this trial, and this is exciting news for our patients with muscle-invasive urothelial carcinoma. I'm hoping that pembrolizumab will be another option for our patients when we are discussing adjuvant immunotherapy in the clinic, moving forward very soon. With that, we have covered several abstracts addressing prostate, bladder, and kidney cancer, significantly influencing our medical practices, at least at the current moment or in the near future. Todd, thank you for sharing your insights today. These are undoubtedly exciting updates for all members of the GU oncology community, and we are grateful for your valuable contribution to the discussion. Many thanks. Dr. Todd Morgan: Thanks, for having me, Neeraj; this was really fun. I'm just really proud and excited to still be part of this field, to be part of the GU oncology field, and it continues to be exciting for all the folks who are coming up. Dr. Neeraj Agarwal: Indeed. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much.   Disclaimer: The purpose of this podcast is to educate and 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. Guest statements on the 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.   Find out more about today's speakers:   Dr. Neeraj Agarwal @neerajaiims   Dr. Todd Morgan @wandering_gu   Follow ASCO on social media:   @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn       Disclosures:    Dr. Neeraj Agarwal:    Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences    Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas   Dr. Todd Morgan: Consulting or Advisory Role: Myriad Genetics, MDxHealth, TerumoBCT Research Funding (Institution): Prostate Cancer Foundation, National Institutes of Health, Department of Defence, GenomeDX Biosciences, Myriad Genetics, MDxHealth  

A truly great Christmas tradition is when Toni Choueiri and his merry band of GU Oncology Fellows at Dana Farber, drop their list of the Top 10 GU Oncology papers of the year. And true to form, Toni's tweet on Christmas Day contains an immaculate list of GU highlights of 2023. A great mixture of tumour types, some brave choices with a Phase 1 study and a negative trial in there. And all the details beautifully summarised in their twitter thread (link below).  And as ever, Declan and Renu were delighted to welcome Toni back to GU Cast to further disseminate this great list and discuss highlights and controversies. Even better on our YouTube channel Links:Toni's tweet with Top 10 GU Onc papers of 2023 

We describes progress in system therapy for advanced papillary RCC. Opportunities and challenges around personalised therapy are discussed

Discussing GU (Genitourinary) Cancer ASCO 2023 Highlights, focusing on practice changing studies with Dr. Toni Choueiri, Director, Lank Center for Genitourinary Oncology and Professor of Medicine at Harvard Medicine School - Dana-Farber Cancer Institute. Covering four important studies: - TALAPRO-2: Ph3 study of talazoparib + enzalutamide vs placebo + enzalutamide as first-line (1L) treatment for mCRPC with homologous recombination repair (HRR) gene alterations - CLEAR: 4-year follow-up of lenvatinib plus pembrolizumab vs sunitinib in pts with advanced renal cell carcinoma - CONTACT-03: efficacy and safety of atezolizumab plus cabozantinib vs cabozantinib alone after progression with prior checkpoint inhibitor in metastatic renal cell carcinoma - THOR: Erdafitinib vs chemo in pts with advanced or metastatic urothelial cancer with select FGFR alteration

Toni Choueiri describes the results of this renal cancer trial exploring rechallange with immune therapy

Toni Choueiri and Brian Shuch discuss Belzutifan alone and in combination for VHL syndrome and advanced sporadic RCC

Toni Choueiri, M.D., is the Director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute (DFCI). He is the Co-leader of the Kidney Cancer Program and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School. He has received the George Canellos Award for Excellence in Clinical Investigation and Patient Care, the Eugene Schonfeld Award from the Kidney Cancer Association, and last year he was inducted into the prestigious Giants of Cancer Care. He has over 675 PubMed indexed publications and is the lead investigator of multiple, national, and international phase I-III trials in GU cancers. “A great physician is not measured by the number of publications or how fast you become a professor or the awards you have received. A great physician is measured by people saying (not in your presence) -  ‘I want to send my mom to this person.' That to me is a great physician.” Tune into another conversation on The Medicine Mentors as we talk about rediscovering ourselves, building trust, and aiming for peak performance in medicine with Dr. Toni Choueiri. Pearls of Wisdom:   1. There is no one path to success; the path differs for everyone, and so rather than having a tunnel vision, we should be honest with ourselves and keep our mind open to all possibilities so that we can really find what makes our heart palpate. 2. We are all going to face scenarios where a patient needs our help and at the same time we have a call from our family or a meeting for our research project, or an issue in the lab. The question is what comes first, and categorically the patient should always come first and should be the priority. 3. We should ask ourselves: ‘Am I a doctor that my physician friends would send their mom or a loved one to?' And its really when we start to continually raise the bar for our personal performance that we move to the next level.

Featuring perspectives from Prof Laurence Albiges, Dr Toni Choueiri and Prof Thomas Powles, moderated by Dr Brian Rini, including the following topics: •      Available Data with and Ongoing Investigation of Immune Checkpoint Inhibitors for Nonmetastatic Renal Cell Carcinoma (RCC) — Prof Powles  o   Introduction (0:00) o   Case: A woman in her early 60s after left nephrectomy (T3aN0M0 clear cell carcinoma) — Swati Vishwanathan, MD (1:39) o   Cases: A man in his early 50s develops renal dysfunction after 2 cycles of adjuvant pembrolizumab for RCC and a man in his late 60s with Stage III clear cell RCC (ccRCC) discontinues adjuvant pembrolizumab due to severe musculoskeletal pain and joint swelling — Justin Peter Favaro, MD, PhD and Priya Rudolph, MD, PhD (6:05) o   Faculty presentation: Prof Powles (11:03) •      Evidence-Based Selection of First-Line Therapy for Metastatic RCC — Dr Choueiri  o   Case: A man in his early 70s with metastatic RCC enrolls on the PDIGREE trial and receives nivolumab/ipilimumab without response followed by cabozantinib — Helen H Moon, MD (21:32) o   Cases: A man in his early 70s receives ipilimumab/nivolumab for widely metastatic RCC and develops autoimmune hepatitis and a man in his early 60s with metastatic ccRCC receives ipilimumab/nivolumab followed by nivolumab with response but develops hypothyroidism and hypoadrenalism — Victoria Giffi, MD and Philip L Brooks, MD (25:33) o   Faculty presentation: Dr Choueiri (36:38) •      Treatment Options for Relapsed/Refractory RCC — Dr Rini  o   Case: A woman in her early 60s with metastatic ccRCC receives lenvatinib/pembrolizumab but develops difficult-to-manage hypertension — Eric H Lee, MD, PhD (46:04) o   Case: A woman in her mid 60s with metastatic ccRCC and somatic VHL gene mutation receives ipilimumab/nivolumab and develops a solitary brain metastasis — Sunil Gandhi, MD (52:36) o   Faculty presentation: Dr Rini (57:54) •      Management of RCC Among Special Patient Populations — Prof Albiges  o   Case: A man in his late 60s with Waldenström macroglobulinemia and metastatic papillary RCC receives first-line ipilimumab/nivolumab followed by nivolumab but develops disease progression, including brain metastases — Nikesh Jasani, MD (1:07:58) o   Case: A woman in her early 70s with a history of psoriatic arthritis develops metastatic ccRCC, receives pembrolizumab/axitinib and develops elevated liver function tests — Georges Azzi, MD (1:12:38) o   Faculty presentation: Prof Albiges (1:18:45) CME information and select publications

Guest host Dr. Neeraj Agarwal and Dr. Christian Kollmannsberger discuss practice-changing abstracts that were presented at the 2023 ASCO Genitourinary Cancers Symposium, including results from the TALAPRO-2, PROpel, TRITON3, ARASENS, KEYNOTE-057, CheckMate 274, and CheckMate 9ER studies. TRANSCRIPT Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, and professor of Medicine at the Huntsman Cancer Institute at the University of Utah, and editor-in-chief of the ASCO Daily News.  Today, we will be discussing practice-changing abstracts and other key advances in GU Oncology featured at the 2023 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Christian Kollmannsberger, the chair of this year's ASCO GU. Dr. Kollmannsberger is a GU medical oncologist at the BC Cancer Vancouver Cancer Center and a clinical professor at the University of British Columbia.  Our full disclosures are available in the transcript of this episode, and the disclosures of all guests on the podcast can be found on our transcripts at asco.org/DNpod.  Christian, thank you for joining us on the podcast today.  Dr. Christian Kollmannsberger: Thank you very much, Neeraj. It's a real pleasure to be here and have this discussion. Dr. Neeraj Agarwal: Thank you. So, Christian, the GU meeting featured remarkable progress in various GU malignancies. Could you please share some of the prominent topics that made the headlines this year and give us an overall feel of ASCO GU this year? Dr. Christian Kollmannsberger: Absolutely. I think it was a great meeting with over 5,800 attendees from more than 70 countries. And most of the attendees were in person, so it was a great event. ASCO GU is truly the premier global event to feature the very best of GU cancer research and treatment. The theme of this year's meeting was "Today's Science, Tomorrow's Treatment," and that was reflected in the novel scientific and clinical findings that were presented and will potentially lead to changes in our daily clinical practice. It also reminds us how quickly the development today is and how quickly novel scientific progress is immediately translated into clinical practice, particularly oncology.   I was very impressed by the meeting's emphasis on diversity, interactivity, networking, multidisciplinary collaboration, and evidence-based care. We introduced several new features such as a “Meet the Professor session, a women's networking event, etc. And the first day really kicked off with a very rich focus on prostate cancer and much attention given to PARP inhibitors in our first session. As an example, LBA 17 was the first late-breaking abstract presented. And congratulations to you, Neeraj, on delivering this exciting data on the TALAPRO-2 trial, which were eagerly awaited. Let's start with that. Can you tell us about this trial? Dr. Neeraj Agarwal: Yes, of course. So the TALAPRO-2 trial was a phase 3 randomized trial where patients in newly diagnosed metastatic CRPC settings were randomized to standard of care enzalutamide plus placebo versus enzalutamide plus talazoparib PARP inhibitor. And as we know, Christian, the rationale has been that dual inhibition of PARP and AR may enhance the efficacy of each. And there's a laboratory preclinical rationale and based on which other studies have been done in the past. So, without getting into too much detail into the rationale for the trial, I'll come right to the results of the trial. So, this was the first-line mCRPC setting where rPFS was the primary endpoint as assessed by the independent radiology assessment. And in this trial, patients were recruited regardless of the homologous recombination repair gene alterations. So, patients were recruited and they were prospectively tested for whether they had these HRR gene alterations or not, but all comer population was included in this trial. And after a median follow-up of approximately 23 months, the trial read out, and we found that trial made the primary endpoint was improved radiographic progression-free survival with the rPFS being about 22 months in the enzalutamide arm and not reached in the combination arm with a 37% reduction in risk of progression or death.  If you look at the subgroup analysis of patients who were HRR+, there was a 54% reduction risk of progression or death. If you look at patients who were stratified in HRR- or unknown group, there was a 30% reduction risk of progression or death. If you specifically look at an exploratory analysis we did to look for patients who were HRR- by prospective tumor tissue testing; there was a 34% reduction in risk of death with a hazard ratio of 0.66 favoring the combination arm. So overall, the rPFS primary endpoint was met in all groups. We also see significant delay in PSA progression in the combination arm by more than nine months. We also see delays in the time to cytotoxic chemotherapy. We saw delay in progression or death on subsequent neoplastic therapy after the protocol treatment. We saw delays in deterioration of quality of life and global health status. All these were significant and happened on the talazoparib plus enzalutamide arm.  So overall, if you look at the totality of the data, these all favored the combination of talazoparib plus enzalutamide compared to enzalutamide alone. I want to highlight that overall survival is immature at 31% maturity with a hazard issue of 0.89, currently favoring enzalutamide plus talazoparib. But we'll have to look at more mature data as time passes.  Dr. Christian Kollmannsberger: Wow. Thank you, Neeraj. So, it sounds like that was a very positive trial, and it's potentially practice-changing. One of the concerns is always safety and toxicity. So can you tell us whether there were any new safety signals, and can you tell us more about the common adverse events that were noticed in TALAPRO-2? Dr. Neeraj Agarwal: No discussion is complete without talking about safety results, so I'm glad you asked me, Christian. The most common dose-affecting toxicity, if you will - so toxicities which led to dose modification and dose discontinuation of talazoparib were cytopenias, as we expect from this class of agents. So anemia, neutropenia, thrombocytopenia, these were the common toxicities. In fact, rate with anemia was 46.5%. Neutropenia and cytopenia were much less common.  I would like to highlight one fact which also came up during the discussion section after our oral presentation. The qualifying criteria for entry in this trial was a hemoglobin of 9-gram percent. And 49% of patients had grade 1 to 2 anemia at baseline, that is before starting treatment with talazoparib. So, we knew that if you mandate dose reduction, a lot of patients will not get adequate dosing of talazoparib. So, we waited for grade 3 anemia and then instituted dose reduction. And that I thought personally was a good strategy because the grade 3 anemia happened after a median duration of three months, 3.3 months to be more precise. And then, these patients underwent protocol-mandated dose reduction, following which the dose discontinuations were quite low actually. Only 8.3% patients discontinued talazoparib because of anemia, and the median dose intensity or median relative dose intensity of talazoparib in the talazoparib arm remained quite high at more than 80%, which translates to a talazoparib dose of 0.4 milligram daily when the starting dose was 0.5 milligram. So those were the hallmark of toxicities.   I do like to mention that those grade 3, 4 toxicities which are more known to affect the quality of life of our patients, such as grade 3, 4 anorexia, fatigue, nausea and vomiting, they were quite rare, happening in 1 to 4% patients who were on talazoparib. So overall, regarding the side effects, they were manageable, there were no new safety signals, and we could maintain adequate talazoparib dosing with dose reduction, which happened quite early during the protocol treatment.  Dr. Christian Kollmannsberger: Thank you, Neeraj. Very impressive results indeed. The patient population included in TALAPRO-2 was very similar to those included in the PROpel phase 3 trial, which tested the combination of abiraterone and olaparib in the first-line mCRPC setting. So, I'd like to just mention that we also saw LBA16 on the PROpel study, which was the final overall survival in PROpel, which was presented by Noel Clarke. So PROpel, as you know, was a randomized phase 3 trial evaluating efficacy and safety of olaparib plus abiraterone versus placebo plus abiraterone as first-line therapy for mCRPC in the first-line metastatic castration resistance setting. The enrollment in that study was independent of known defects in the homologous recombination repair gene pathway in contrast to other studies, such as MAGNITUDE, which tested the biomarker upfront. A total of 796 patients were randomly assigned to either olaparib plus abiraterone or placebo plus abiraterone. And we saw similar results, significant radiographic progression-free survival with olaparib plus abiraterone in PROpel, which was the primary endpoint similar to TALAPRO-2, and that was published last year in the New England Journal of Medicine Evidence.  Now, this abstract presented here at ASCO GU reported on overall survival with an overall survival majority of 47.9% and showed that with the addition of the PARP inhibitor olaparib to abiraterone, a statistically non-significant but clinically meaningful improvement in overall survival of about seven months were achieved compared to standard of care in abiraterone alone. The numbers were 42.1 versus 34.7 months in the all-comers population of patients in the first-line mCRPC setting. Importantly, I think the median overall survival of more than 42 months really represents the longest reported median overall survival thus far in a phase III trial for first-line metastatic castration-resistant prostate cancer. Although the median overall survival for the non-HRR group remains not statistically significant, with a hazard ratio of 0.89. Dr. Neeraj Agarwal: Such a great synopsis of the PROpel result data. Thank you, Christian, for highlighting these results. As we know, the combination is already approved by the EMA, the European Medical Agency, for patients in the first-line mCRPC setting who are not candidates for docetaxel chemotherapy. If this combination is approved by the FDA, we may have one more therapeutic option for our patients in first-line mCRPC.  So, just continuing on the PARP inhibitors, there was one more oral presentation with PARP inhibitor rucaparib by Dr. Alan Bryce from the Mayo Clinic, Arizona. This was Abstract 18 on the primary result of the TRITON3 trial. So to complete our PARP inhibitor section, I would like to summarize the result of the TRITON3 trial, which was a randomized phase III trial evaluating rucaparib versus physician choice, which notably included docetaxel in addition to abiraterone or enzalutamide in patients with chemotherapy-naive mCRPC with BRCA1, BRCA2 or ATM alterations. These patients had disease progression after having one novel hormonal therapy, or we call them second-generation androgen pathway inhibitors in any setting. So these patients had to have disease progression on a novel hormonal therapy.   In the BRCA subgroup and the subsequent intention to treat the population, the primary endpoint tested first was radiographic progression-free survival, and overall survival was the key secondary endpoint. The subgroup of patients with BRCA-altered disease had a median rPFS of 11.2 months with rucaparib compared to 6.4 months with physician choice of treatment - looks like almost doubling of the rPFS with the rucaparib. In the overall ITT population, median rPFS was 10.2 months with rucaparib and 6.4 months with the physician's choice of treatment. Although the overall survival data are immature, we still see a trend for improved overall survival with rucaparib. Regardless, the study clearly demonstrates the value of rucaparib for treating BRCA1 and BRCA2-altered mCRPC after disease progression on an androgen receptor pathway inhibitor. So these were the impressive results from the TRITON3 trial.  But before we switch to non-prostate abstract, I would like to complete the prostate cancer discussion by talking about the Abstract 15, which was based on the results of the ARASENS trial presented by Dr. Maha Hussain. As we know, ARASENS is a randomized phase 3 trial evaluating the efficacy and safety of darolutamide plus androgen deprivation therapy plus docetaxel versus androgen deprivation therapy or ADT plus docetaxel. So the triplet of ADT plus darolutamide plus docetaxel being compared to ADT plus docetaxel chemotherapy in patients with newly diagnosed metastatic castration-sensitive prostate cancer. A total of 1,300 patients were randomly assigned to the doublet versus triplet. As presented in the last ASCO GU meeting exactly one year ago, the primary endpoint of the study was met with a significant improvement in overall survival and a 32% reduction in risk of death for patients on the triplet therapy with ADT plus docetaxel plus darolutamide versus ADT plus docetaxel chemotherapy. So triplet therapy was already approved based on these data.  The abstract presented by Dr. Hussain this year is a post-talk analysis where Dr. Hussain and colleagues investigated the impact of triplet therapy across patients with high volume versus low volume per chartered criteria and higher risk versus low risk using latitude trial criteria. And investigators knew that these results would be highly attractive to practicing oncologists who are now choosing treatment based on volume of disease or risk of disease, more commonly, volume of disease.  So, let's come to what was presented this ASCO GU. So, after 1,305 patients in ARASENS, the majority had high-volume disease and high-risk disease. Among patients with high-volume disease, the addition of darolutamide reduced the risk of death by 30% compared with ADT and docetaxel, with a hazard ratio of 0.69. In the risk groups, the addition of darolutamide seems to favor both high-risk and low-risk groups. Among patients with low-volume disease, there was a trend towards improvement in overall survival with the addition of darolutamide, but it did not reach statistical significance. The great news was that there was no new safety signal. So, to summarize these data, the triplet of darolutamide plus ADT plus docetaxel showed superior overall survival compared to doublet of ADT plus docetaxel, with an important caveat that triplet was not compared with any of the modern doublets of ADT plus a second generation androgen receptor pathways inhibitor such as abiraterone, apalutamide, or enzalutamide, or even darolutamide. So, I wish there was a third arm of ADT plus darolutamide.  Having said that, triplet can be considered a standard of care now based on these data for patients with metastatic hormone sensory prostate cancer, where we would be using ADT plus docetaxel chemotherapy. And from this meeting data, this efficacy of triplet can be applied to high-volume disease and all risk disease. And we just need more time to see how the data pans out in low-volume patients with metastatic hormone-sensitive prostate cancer.  Dr. Christian Kollmannsberger: Yes, I completely agree, Neeraj. I think all the data presented in these abstracts are really impressive and will impact our daily clinical practice and our patients more or less immediately. I think the use of PARP inhibitors, whether as a monotherapy or in combination with androgen receptor pathway inhibitors, as well as now the option of triplet therapy in the metastatic castration sensitive setting really offer patients with metastatic prostate cancer new treatment strategies and most importantly, improved survival outcomes. And it is impressive to see how we have pushed the prognosis and the outcomes for our patients with prostate cancer, I would say, in the last five to ten years. And similar to last year, I think the entire Prostate Cancer Day at ASCO GU 2023 was full with impressive data and featured dynamic content throughout the day. Dr. Neeraj Agarwal: Indeed. So, let's move on to bladder cancer. Christian, what are your key takeaways from the bladder cancer studies presented at the meeting? Dr. Christian Kollmannsberger: I think there were interesting abstracts in both the non-muscle-invasive and the muscle-invasive setting and the metastatic setting. So, for example, Abstract 442 was presented by Dr. Andrea Necchi on the cohort B of the phase 2 KEYNOTE-057 trial. As a background here, the standard treatment for high-risk non-muscle-invasive bladder cancer involves transurethral resection of the bladder tumor, a TURBT, followed by intravesical BCG therapy to eradicate any residual disease. And patients who fail to adequately respond to BCG are usually recommended to undergo radical cystectomy. So in the cohort B of the phase 2  KEYNOTE-057 trial that investigated the safety and efficacy of pembrolizumab as a single agent for patients with BCG-unresponsive, high-risk non-muscle-invasive bladder cancer who were ineligible or declined to undergo radical cystectomy, enrolled patients received standard-dose pembrolizumab of 200 milligrams every three weeks for up to 35 cycles. So very common as we do it with other disease sites. And at a median follow-up of 45.4 months, the primary endpoints of disease-free survival at twelve months was 43.5%. The median disease-free survival duration was 7.7 months. These are encouraging results, and we should keep in mind that a radical cystectomy has immense impact on our patients' quality of life. So I think it is important that we do these trials.  Now in order to address potential biases in this phase II trial, such as the underlying heterogeneity of transurethral resection of bladder tumor quality, and to obtain a more comprehensive understanding of pembrolizumab's efficacy relative to a particular control group, we need further evaluation of pembrolizumab in a randomized trial before we can really go for regulatory approval. But overall, I think for the first time in a long time that we seem to be able to move the needle in non-muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Thank you, Christian, for this great overview. Could you please also share the findings presented by Dr. Matt Galsky on Abstract 443? Dr. Christian Kollmannsberger: Of course, Neeraj. Abstract 443, presented by Matt Galsky, reported the extended follow-up results from the CheckMate 274 trial, which looked at another very important field where we haven't made that much progress, which is the adjuvant setting. And CheckMate 274 examined adjuvant nivolumab compared to placebo for patients with high-risk resected muscle-invasive urothelial carcinoma. In this trial, nivolumab was given at 240 milligrams every two weeks or placebo every two weeks for up to one year of treatment. After following up with patients for a median of 36.1 months, the study found that those who received nivolumab had a median DFS of 22 months compared to only 10.9 months for those who received placebo among the ITT patients. So basically, a doubling of the DFS with the addition of adjuvant nivolumab.  The results were particularly notable for patients with high PD-L1 expressions or PD-L1 expression of 1% or more, as those who are treated with nivolumab had a median DFS of 52.6 months, which was six times higher than the DFS in the control group where patients received placebo, which was only 8.4 months. And I think that is truly impressive. One year of adjuvant therapy with nivolumab continues to show a sustained disease-free survival benefit over a period of three years in both the ITT and the PD-L1-high patient population. In my view, these results reinforce the utility of nivolumab in the adjuvant urothelial carcinoma setting after surgery. And it will be interesting to see how the overall survival pans out in this study.  So, Neeraj, moving on to kidney cancer, what were your key takeaways from these studies on kidney cancer presented in this meeting?  Dr. Neeraj Agarwal: So, there were exciting results presented from multiple studies in this area as well. For example, Abstract 603 presented by Dr. Mauricio Burotto, senior author was, Dr. Toni Choueiri on the three-year follow-up from the phase 2 CheckMate-9ER trial. So, in this trial, patients were randomized one-to-one to nivolumab 240 milligrams every two weeks, plus cabozantinib 40 milligrams daily versus sunitinib 50 milligrams daily for four weeks, and it was a six-week cycle for sunitinib until disease progression or unacceptable toxicity. So this was the design of the phase 3 CheckMate-9ER trial. And after a median follow-up of three years, the benefit of nivolumab plus cabozantinib remained consistent with previous follow-ups. So, as we know, these data have been presented in the past, also published in the New England Journal of Medicine. But this meeting was a clear follow-up of these data.  Notably, the median overall survival of patients treated with cabozantinib plus nivolumab in the ITT population, which included all favorable intermediate and poor IMDC score patients, was significantly improved at 49.5 months compared to 35.5 months in the sunitinib arm. It is so heartening to see that median overall survival breaching the four-year mark in our patients with metastatic RCC in a consistent fashion. We saw similar data with the combination of ipilimumab plus nivolumab recently. And as these trials are maturing, we are probably going to see more combinations breaching this four-year mark. So importantly, no new safety signals emerged with the additional follow-up in either arm. And I think these results provide further support for the use of cabozantinib plus nivolumab as a first-line treatment option for patients with metastatic or advanced renal cell carcinoma. Dr. Christian Kollmannsberger: Indeed, I think it is extremely impressive what we've seen over the last 15 years in metastatic kidney cancer, going from a median overall survival of about a year to now more than four years. I think that is a great achievement, and we can see it on a daily basis in our clinical practice.  Now, before we wrap up, I would like to highlight another potentially practice-changing trial, LBA602, which titled, “Results from Phase 3 Study of 89Zr-DFO-Girentuximab for PET/CT Imaging of Clear Cell Renal Cell Carcinoma: The ZIRCON Trial” presented by Dr. Brian Shuch. The background of this is that the detection of renal masses poses a challenge due to the limitations of diagnostic options such as imaging and biopsy. And we often, in clinical practice, are confronted with "What exactly is this?" And what's even more importantly, “What's the histology of this?” And a non-invasive, accurate method is needed for pre-treatment risk stratification. Girentuximab, a monoclonal antibody that targets carbonic anhydrase IX expressed on clear cell renal cell carcinoma, can obviously now aid in the differentiation between clear cell renal cell carcinomas and other renal lesions when radiolabeled with this new agent.  The ZIRCON trial was open-label and designed to include patients with renal masses up to 7 cm in size or clear tumor stage cT1 who were scheduled for partial nephrectomy within 90 days of planned TLX250-CDx administration. The enrolled patients received a single intravenous dose of girentuximab on day 0 and underwent FDG PET/CT imaging on day 5 before their scheduled surgery. And the co-primary endpoints were to assess the sensitivity and specificity of girentuximab PET/CT imaging for detecting clear cell renal cell carcinoma in patients with indeterminate renal masses, with histology as the reference standard, which I think is a great way to test these agents because you get 100% validation.  In the primary analysis of 284 patients, the average sensitivity and specificity across all three central readers were 86% and 87%, respectively, exceeding the prespecified thresholds. The positive and negative predictive values were 93.4% and 78%, respectively. And with very few related adverse events reported, the study affirms that girentuximab PET/CT is safe and effective in identifying clear cell renal cell carcinoma in patients with indeterminate renal masses. And the findings hold potential for developing optimal management strategies for patients with indeterminate renal masses. I think this is important that we add a non-invasive method to this because we are confronted on a regular basis with patients who either cannot tolerate a biopsy or where the biopsy is indeterminate. And this could potentially be a great tool to help us with our pre-treatment planning of our treatment strategy. Dr. Neeraj Agarwal: Wow. So, it looks like a new PET scan using a unique tracer and antibody to detect the clear cell renal cell carcinoma with high specificity and sensitivity. It reminds me of drawing a crude analogy from the PSMA PET scan in prostate cancer. And hopefully, we will be able to use these newer scans that we call TLX250-CDx PET/CT scan. I hope they have a simpler name for this very soon. Or maybe follow up for patients who had kidney cancer, localized kidney cancer taken out by radical surgery, and then we are following them. And sometimes, we don't know if a small lung nodule is metastatic or not. And these kinds of imaging studies may help us down the line in monitoring those patients as well. So indeed, very exciting progress not only in the therapeutic area now but also in diagnostic fields at this GU ASCO.   So with that, we have seen multiple abstracts on prostate, bladder, and kidney cancer with real impact on how we practice medicine. Thank you, Christian, for sharing your insight with us today. It is an exciting time in GU Oncology, and we appreciate you taking the time to contribute to the discussion. Thank you so much.   Dr. Christian Kollmannsberger: Thank you, Neeraj, thank you for having me. And I completely agree it remains an exciting time in GU oncology.   Dr. Neeraj Agarwal: And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcripts of this episode.  Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the 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.   Find out more about today's speakers:   Dr. Neeraj Agarwal  @neerajaiims Dr. Christian Kollmannsberger Follow ASCO on social media:    @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn    Disclosures:   Dr. Neeraj Agarwal:    Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences   Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, Arvinas   Dr. Christian Kollmannsberger: None disclosed  

Toni Choueiri, MD (Dana-Farber Cancer Institute, Harvard), discusses the latest research in kidney cancer presented at the 2023 ASCO Genitourinary Cancers Symposium. Also, regular contributor Dr. MedLaw explains all you need to consider and do, as well as not do, in the delicate situation of having to report a colleague.Let us know what you thought of this week's episode on Twitter: @physicianswkly Want to share your medical expertise, research, or unique experience in medicine on the PW podcast? Email us at editorial@physweekly.com! Thanks for listening!

Featuring a slide presentation and related discussion from Dr Toni Choueiri, including the following topics: Evolution in the management of renal cell carcinoma (RCC) (0:00) Adjuvant therapy for intermediate- or high-risk RCC (1:52) Front-line therapy for patients with metastatic RCC (8:39) New agents for the treatment of relapsed or refractory RCC (16:24) Mechanism of action and efficacy of HIF2-alpha inhibitors for von Hippel-Lindau-associated RCC (19:56) CME information and select publications

Featuring an interview with Dr Toni Choueiri, including the following topics: Case: A woman in her early 70s with a large kidney tumor and multiple pulmonary nodules (0:00) Case: A woman in her early 60s diagnosed with metastatic clear cell renal cell carcinoma (RCC) (12:52) Approach to adjuvant treatment for RCC (16:14) Examining differences between PD-1 and PD-L1 inhibitors (20:09) Management of non-clear cell RCC (24:10) Challenges in identifying patients with RCC who are more likely to benefit from immune checkpoint inhibitors (28:22) Mechanisms of action of HIF2-alpha inhibitors for von Hippel-Lindau-associated RCC (30:31) Future directions in the care of patients with RCC (36:24) CME information and select publications

Dr Toni Choueiri from Dana-Farber Cancer Institute in Boston, Massachusetts, discusses recent therapeutic advances in the care of patients with renal cell carcinoma. CME information and select publications here (http://www.researchtopractice.com/OncologyTodayRCC22).

Featuring a discussion on recent advances in the treatment of renal cell carcinoma with Dr Toni Choueiri, moderated by Dr Neil Love.

Discussing practice-changing Genitourinary (GU) Cancer studies presented at the European Society of Medical Oncology 2022 with Dr. Toni Choueiri, Chief - Director, Lank Center for Genitourinary Oncology and Professor of Medicine at Harvard Medicine School - Dana-Farber Cancer Institute.

Bob Figlin, MD, and Toni Choueiri, MD, the director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, discuss the early results from the COSMIC-313 trial, which Dr. Choueiri presented at ESMO 2022. The trial enrolled previously untreated patients with metastatic clear cell renal cell cancer who were classified as intermediate- to poor-risk. Standard of care doublet therapy, nivolumab (nivo) plus ipilimumab (ipi), was compared with triplet therapy, consisting of nivo-ipi plus cabozantinib. Triplet therapy improved progression-free survival compared with doublet therapy, specifically in the intermediate-risk group. Dr. Choueiri also discussed the complicated landscape in RCC and how practicing oncologists can evaluate patients for appropriate treatments as well as how to communicate effectively with patients about the factors that contribute to that decision.

OncBrothers are back with the latest installment!  Dr. Toni Choueiri, Director @ Lank Center for Genitourinary Oncology and Professor of Medicine at Harvard Medical School discuss the latest updates in the treatment of GU cancers highlighted at ESMO.

Toni Choueiri describes the study.

Catch up on our highlights from Day 4 of ESMO 2022! We spoke to Toni Choueiri, Erika Hamilton, Jonathan Rosenberg,... The post ESMO 2022 Daily Round-Ups: Day 4 appeared first on VJOncology.

Catch up on our highlights from Day 4 of ESMO 2022! We spoke to Toni Choueiri, Erika Hamilton, Jonathan Rosenberg,... The post ESMO 2022 Daily Round-Ups: Day 4 appeared first on VJOncology.

Nick Pannoni , 62, renal cell carcinoma (kidney cancer), Forestdale, with Dr. Toni Choueiri, Director of the Lank Center for Genitourinary Oncology, Dana-Farber

Anne Gross, PHD, RN, Senior Vice President and Chief Nursing Officer, Dana-Farber● Anne Gross, PhD, RN is senior vice president for patient care services and chiefnursing officer. There are more than 700 registered nurses, nurse practitioners,clinical specialists, and nurse scientists working at Dana-Farber.● Anne can give insight into the challenges overcome by the amazing nursing staffduring the COVID pandemic. What they have done and achieved since 2020 inspiresher and keeps her optimistic for the future.● She can also provide insight about the often emotionally powerful relationshipnurses form with patients and why it's a unique nursing career.● Since 2020, along with continuing to provide cancer treatment, oncology nurses hadthe added challenge of protecting patients and each other from COVID hrough strictisolation procedures and the use of personal protective equipment (also known asPPE).● The nurse acquired new skills to care for immunocompromised patients in specialCOVID intensive care units.● In other settings, oncology nurse navigators transitioned their practice to be remoteso they could care for patients while they were in their homes through telehealthvisits and clinical trial nurses innovated standard operations, such as shippinginvestigational drugs to patients' homes, to enable them to safely remain on theirstudies.● Anne takes great pride in Dana-Farber's nursing and patient care services staff andthe patient experience at Dana-Farber remains as strong as ever: As a patient youare never alone.● Anne leads a nursing staff focused on the future:○ Continuing to manage through the lingering threats of the pandemic whilefocusing on building a pipeline for the future○ Addressing the national nursing shortage with the goal of training the nextgeneration of oncology nurses ○ Expanding access to our care by opening Foxborough location and expandingSouth Shore Nick Pannoni (PAH-NO-NEE), 62, renal cell carcinoma (kidney cancer), Forestdale, with Dr. ToniChoueiri (SHWERRY), Director of the Lank Center for Genitourinary Oncology, Dana-Farber● Six years ago, Nick, a father of four, was diagnosed with prostate cancer, but it wascaught early enough where doctors only needed to remove his prostate for him to bedeclared cancer-free.● Unfortunately, three years later, cancer had returned, but this time it was acompletely different type of cancer: kidney cancer. Specifically known as renal cellcarcinoma, Nick's left kidney was removed as it had been encased in the cancer.● Once Nick recovered, his oncologist Dr. Steven Chang mentioned that he may wantto see Dr. Toni Choueiri, the lead author of the KEYTRUDA study.● Nick entered the clinical trial as a double-blind participant, meaning he would notknow if he received the medication or a placebo. Though there isn't a way to know for sure, Nick believes he received the drug as he experienced several of thecommon side effects.● Once high-risk, there is now no evidence of disease. Nick continues to move forwardand live his everyday life. He gets blood work and scans every four months, but onlyto make sure that cancer has not come back.

Nick Pannoni, 62, renal cell carcinoma (kidney cancer), Forestdale, with Dr. ToniChoueiri, Director of the Lank Center for Genitourinary Oncology, Dana-Farber● Six years ago, Nick, a father of four, was diagnosed with prostate cancer, but it wascaught early enough where doctors only needed to remove his prostate for him to bedeclared cancer-free.● Unfortunately, three years later, cancer had returned, but this time it was acompletely different type of cancer: kidney cancer. Specifically known as renal cellcarcinoma, Nick's left kidney was removed as it had been encased in the cancer.● Once Nick recovered, his oncologist Dr. Steven Chang mentioned that he may wantto see Dr. Toni Choueiri, the lead author of the KEYTRUDA study.● Nick entered the clinical trial as a double-blind participant, meaning he would notknow if he received the medication or a placebo. Though there isn't a way to know for sure, Nick believes he received the drug as he experienced several of thecommon side effects.● Once high-risk, there is now no evidence of disease. Nick continues to move forwardand live his everyday life. He gets blood work and scans every four months, but onlyto make sure that cancer has not come back. Kidney cancer facts● Kidney cancer is a type of cancer that starts in the kidney. Cancer starts when cells inthe body begin to grow out of control.● About 79,000 new cases of kidney cancer (50,290 in men and 28,710 in women) willbe diagnosed in 2022.● Kidney cancer is about twice as common in men than in women.● Most people with kidney cancer are older. The average age of people when they arediagnosed is 64 with most people being diagnosed between ages 65 and 74. Kidneycancer is very uncommon in people younger than age 45. Dr. Toni Choueiri● Dr. Toni Choueiri is the Director of our Genitourinary (GU) Oncology Disease Centerand the Lank Center for Genitourinary Oncology.● Dr. Choueiri can speak about the challenges of treating kidney cancers and theimportance of clinical trials.● He is the lead investigator of multiple national and international phase one, two andthree trials in GU cancers.● Dr. Choueiri is interested in developing novel therapies (including immunotherapies)and biomarkers in GU malignancies, including kidney cancer. His research alsofocuses on epidemiology, diagnosis and treatment outcomes of GU cancers usinglarge scale approaches such as meta-analyses from available published trials ornational databases.

Guest host Dr. Neeraj Agarwal, of the University of Utah Huntsman Cancer Institute and the ASCO Daily News editor-in-chief, discusses key therapeutic advances in mRCC and mUC, as well as new research that proposes periodic scans to monitor patients with mCSPC for disease progression, with Dr. Jeanny-Aragon-Ching of the Inova Schar Cancer Institute.  Transcript:  Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News.  My guest today is Dr. Jeanny Aragon-Ching, who is a medical oncologist and the Clinical Program Director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia.  Today, we will be discussing key posters in genitourinary (GU) oncology that will be featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcast.  Jeanny, it is great to have you on the podcast today.  Dr. Jeanny Aragon-Ching: Thanks, Neeraj. It's a pleasure for me to be here as well.  Dr. Neeraj Agarwal: Jeanny, let's begin with Abstract 4510. This is a trial that represents a growing interest among researchers worldwide in the microbiome and how it is impacted by antibiotics and how it modulates immune checkpoint inhibitor response. Can you tell us about this study?  Dr. Jeanny Aragon-Ching: Thanks, Neeraj, I would be happy to. So, the title of the abstract is, “Characterization of the Microbial Resistome in a Prospective Trial of CBM 588 in Metastatic Renal Cell Carcinoma Offers Mechanism for Interplay Between Antibiotic Use and Immune Checkpoint Inhibitor Activity.”  So, this is an interesting abstract that originated likely from the observation that getting antibiotics while on checkpoint inhibitors typically results in worse outcomes, perhaps because antibiotics can clear the normal gut flora and thereby increase these pathogenic antibiotic-resistant bacteria.  Now, on the other hand, there were some retrospective studies using a live microbial product called CBM 588, which seems to improve outcomes in patients on checkpoint inhibitors and getting antibiotics.  So, the idea, therefore, is that shifting the genes encoding antimicrobial resistance could result in a better checkpoint inhibitor response. So, this Abstract 4510 is a small study conducted by Dr. Nazli Dizman and Dr. Sumanta (Monty) Kumar Pal, and colleagues, and enrolled 29 metastatic clear cell RCC patients with intermediate or poorest disease. And they were stratified into receiving either nivolumab or ipilimumab compared to nivo/IPI with CBM 588.  Now stool samples were collected at baseline in week 12. And they did this whole metagenome sequencing to analyze a stool microbiome composition, and they also looked at the antibiotic resistance genes for the most common classes of antibiotics.  The results showed an astounding improvement in objective responses. So, 58%, for instance, in nivo/IPI and the CBM 588 arm compared to only 20% in the nivo/IPI arm. And it seems like also the antibiotics resistance genes were also decreased in those getting the CBM 588 alongside nivo/IPI. Therefore, responses were improved by shifting the gut microbiome alone. So, these findings were published actually recently by these authors in Nature Medicine. So, in case anyone wants to take a deep dive, it would be a good interesting read for this dataset.  Dr. Neeraj Agarwal: Very interesting, indeed. Jeanny, what is the main message here for our colleagues?  Dr. Jeanny Aragon-Ching: I think, Neeraj, the key takeaway message is that this is a very provocative proof of concept trial that suggests shifting the gut microbiome has the potential to improve responses to checkpoint inhibitors and outcomes. So, this is a very up-and-coming trial and is seen also across the board in other cancers.  Dr. Neeraj Agarwal: Thanks, Jeanny. Moving on to urothelial cancer, there is a poster that I think is a must-see for our colleagues. This is Abstract 4577 titled, “Defining Platinum Ineligible Patients with Metastatic Urothelial Carcinoma.”  Dr. Jeanny Aragon-Ching: So, Neeraj, what can you tell us about this abstract?  Dr. Neeraj Agarwal: So, over the past few years, there has been a tremendous evolution in the treatment landscape for patients with metastatic urothelial carcinoma. For over 40 years the standard of care for these patients has been cisplatin-based chemotherapy.  However, approximately 50% of patients are cisplatin-ineligible, due to underlying comorbidities, and are offered carboplatin as an alternative. So, although the checkpoint inhibitors pembrolizumab and atezolizumab were approved as first-line therapy for these patients in 2017, the U.S. Food and Drug Administration (FDA) has now restricted the use of first-line pembrolizumab to platinum ineligible patients with metastatic urothelial carcinoma.  The challenge we face as oncologists since the FDA restriction is the absence of a formal definition of platinum ineligibility and the inclusion of this definition in the guidelines. So, in Abstract 4577, Drs. Shilpa Gupta and Jonathan Rosenberg, along with the team present an updated consensus definition for platinum ineligibility based on an online survey of 60 genitourinary oncologists in the United States.  Based on the results from this survey, any patient with metastatic urothelial carcinoma, meeting 1 of the following 5 clinical and or laboratory parameters should be considered platinum ineligible, and these are 1 of the following: an ECOG performance status of 3 or more, creatinine clearance of fewer than 30 mils per minute, or peripheral neuropathy of grade 2 or more, or heart failure class of 3 or more—so, this is NYHA heart failure class of 3 or more—and lastly, the combination of performance status of 2 or more, plus a creatinine clearance of less than 30 mils per minute.  Dr. Jeanny Aragon-Ching: Well, this is a timely update, Neeraj. So, what do you think is a key takeaway from this abstract?  Dr. Neeraj Agarwal: These criteria based on simple and easily available clinical and or laboratory parameters will now allow us to readily define platinum ineligibility in our patients with metastatic urothelial carcinoma, which is a need in busy clinics, both in academic and community settings.  So, I think once published and obviously once endorsed by guidelines, we really would like to be able to use this criterion to quickly define platinum ineligibility in our clinics.  Dr. Jeanny Aragon-Ching: Agree. Yeah.  Dr. Neeraj Agarwal: So, Jeanny, let me switch the gears. PSMA testing is a hot topic this year. And there is an abstract that could potentially have an impact on future guidelines, and how we will practice further down the road.  So, I'm referring to the Abstract 5088 titled, “Predictive Value of Extra Prostatic Disease Detection by Preoperative PSMAPET for Biochemical Recurrence-free Survival in Patients with Otherwise Localized Prostate Cancer and Who are Treated with Radical Prostatectomy.”  So, this is a follow-up analysis of a multicenter prospective phase 3 imaging trial. So, could you please tell us more about this abstract where they are using PSMA PET scan in the preoperative localized prostate cancer setting?  Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, you may recall that the multicenter prospective phase 3 imaging trial that garnered gallium PSMA approval by the FDA was actually based on this study that looked at the intermediate and high-risk patients with prostate cancer undergoing radical prostatectomy and lymph node dissection, and they underwent prior gallium PSMA PET scanning for pelvic nodal metastases prior to surgery.  So, this was actually previously reported by Dr. Calais and group. Now they are reporting on Abstract 5088 as a post hoc analysis of the same population and group of patients looking for extraprostatic disease. And the final pathology was also correlated to look at nodal disease in these patients in order to predict biochemical recurrence, so they follow these patients for biochemical recurrence occurrence.  So, of the 36% of patients who did undergo radical prostatectomy after they underwent PSMA PET scan, about 41% of them recurred with biochemical recurrence, and 40% of them underwent some kind of salvage therapy or some treatment.  What was very interesting was when they looked at the biochemical recurrence-free survival. It was better in those who were PSMA negative, and that recurrence-free survival was easily about 33 months, compared to only about 7.3 months in those who were PSMA-positive scans.  Furthermore, the ones who had the longest and the highest biochemical recurrence-free survival, intuitively, were those who were node-negative and PSMA PET-negative, so probably not surprisingly. And that rate was about 46 months—close to 4 years. Whereas those who are node-positive on final pathology and their PSMA PET was also positive, they only had about 3 months of biochemical recurrence-free survival.  Dr. Neeraj Agarwal: Very interesting. So, it looks like the PSMA PET scan is predicting biochemical recurrence-free survival in localized prostate cancer settings. So, Jeanny, what is the key takeaway from this trial?  Dr. Jeanny Aragon-Ching: I think, Neeraj, the bottom line is that patients with extraprostatic disease that is detected by their preoperative PSMA PET scan does predict strongly a high risk of biochemical relapse, and this can really be an additional tool that clinicians can use to help inform and guide future therapy.  Dr. Neeraj Agarwal: Thanks, Jeanny. The research on preoperative PSMA testing and its implications on future treatment strategies in the setting is going to be really interesting to watch in the very near future.  Dr. Jeanny Aragon-Ching: Yes, absolutely. I really think we should also discuss Abstract 5072, along those lines, the importance really of radiographic monitoring for disease progression in patients with metastatic hormone-sensitive prostate cancer.  Dr. Neeraj Agarwal: Yes, thanks for reminding and this is Abstract 5072. This is a post hoc analysis of the ARCHES trial, titled, “Radiographic Progression in the Absence of PSA Progression in Patients with Metastatic Hormone-sensitive Prostate Cancer.”  During the last several years, we have seen many of these agents typically given for gastric resistant prostate cancer moving upfront to the castration-sensitive prostate cancer setting. This is especially true for androgen receptor access targeting agents such as abiraterone, enzalutamide, and apalutamide, all being now approved for patients with metastatic castration-sensitive prostate cancer.  What is noteworthy from all these trials, and is reported in Abstract 5072, is the use of imaging studies to evaluate disease progression. So, in Abstract 5072, Dr. Andrew Armstrong and Dr. Arun Azad performed a post hoc analysis of the ARCHES trial to investigate the concordance between radiographic progression and the PSA Progression as defined by PCWG2 criteria, or between radiographic progression and any rise in the PSA above nadir, in patients who were being treated with this novel hormonal therapies, in this case, enzalutamide for metastatic castration sensitive prostate cancer.  And as a quick reminder, ARCHES was a phase 3 trial that showed a significant reduction and radiographic progression-free survival and improved overall survival for patients with metastatic castration sensitive prostate cancer treated with enzalutamide plus androgen deprivation therapy (ADT) versus those treated with placebo plus androgen deprivation therapy.  So, very interestingly, the findings from this study indicate that 67% of patients on the enzalutamide plus ADT arm did not have [Prostate Cancer Clinical Trials Working Group 2 criteria] PCWG2-defined prostate-specific antigen (PSA) progression at the time of radiographic progression. And discordance was present in the ADT-only arm as well, where they found 42% of patients on the ADT-only arm had radiographic progression but did not have PCWG2-defined PSA progression.  Interestingly, this discordance of radiographic disease progression was also seen with any rise in the PSA above nadir. And I personally found this information to be very clinically relevant when we are seeing the majority of patients actually experiencing radiographic disease progression, not experiencing PSA progression at the same time.  Dr. Jeanny Aragon-Ching: Yeah, absolutely. I agree with that, Neeraj. So, very interesting data. So, what do you think is the key takeaway message for the clinicians listening to us?  Dr. Neeraj Agarwal: I'll make the message very simple. I think the message is that patients with metastatic castration-sensitive prostate cancer need to be monitored for disease progression with periodic scans, and PSA monitoring alone is not sufficient in the majority of these patients.  Again, we cannot undervalue the role of periodic imaging studies in these patients so that we can timely diagnose them to have disease progression.  Dr. Jeanny Aragon-Ching: I agree with that.  Dr. Neeraj Agarwal: Jeanny, the last abstract I would like to mention before we wrap up the podcast is Abstract 4509, the results from the phase1 live SPARC 001 study. So, can you please tell us more about this study titled, “Phase-1 Live SPARC 001: The Study of Belzutifan in Advanced Solid Tumors,” which is an update of the renal cell carcinoma cohort with more than 3 years of total follow up?  Dr. Jeanny Aragon-Ching: Thanks, Neeraj. So, while the current therapeutic landscape for patients with metastatic clear cell renal cell carcinoma (RCC) has changed dramatically over the past several years, with significant improvement in patient outcomes. Most patients unfortunately still experience disease progression on current treatments.  So, in-depth molecular profiling of clear cell RCC has revealed recurrent loss of function mutations in VHL in actually greater than 90% of patients. So, the VHL protein, as you will recall, is part of the oxygen-sensing pathway, regulating levels of HIF which is hypoxia-inducible factor protein, it's a transcriptional activator that mediates the response to hypoxic conditions. So, HIF-2α is a key oncogenic driver in RCC.  So, previous data you may recall from the phase-1 Live SPARC 001 trial was designed to evaluate belzutifan so, this was a novel HIF-2α inhibitor which showed durable anti-tumor activity and acceptable safety profile in patients with metastatic clear cell RCC.  So, in Abstract 4509, Drs. Jonasch and Toni Choueiri presented updated results from this trial after more than 3 years of follow-up. Of the 55 patients enrolled 16% of patients remained in treatment. And 62% of patients had discontinued treatment because of, unfortunately, disease progression.  The median progression-free survival (PFS) for the total cohort was 14.5 months. And the overall disease control rate was 80%. Forty percent of patients experienced grade 3 treatment-related adverse events with the most frequent ones being anemia and hypoxia.  There were no great 4 or 5 treatment-related adverse events. And these results, therefore, show that belzutifan monotherapy continues to show a high rate of disease control and a safety profile in a heavily treated population of patients with metastatic RCC. So, it is great to see that there were no new safety signals.  Dr. Neeraj Agarwal: Very nice data indeed. So, Jeanny, what is the key takeaway message here for our listeners?  Dr. Jeanny Aragon-Ching: Yeah, I think the message here is that the use of belzutifan monotherapy continues to show efficacy and safety in patients with metastatic clear cell RCC, which have progressed on multiple prior contemporary therapies, and there are phase 3 trials currently underway.  Dr. Neeraj Agarwal: Jeanny, any final thoughts before we wrap up the podcast today?  Dr. Jeanny Aragon-Ching: Thanks, Neeraj. I think it's a really exciting time to be in genitourinary (GU) oncology, and I'm truly looking forward to seeing some great sessions at the 2022 ASCO Annual Meeting.  Dr. Neeraj Agarwal: Thank you, Jeanny, for sharing your insight with us today. It was a great conversation. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcast.    Disclosures:   Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, Arvinas  Dr. Jeanny Aragon-Ching:   Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc  Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, AstraZeneca/MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis  Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb , Astellas/Seattle Genetics  Travel, Accommodations, Expenses: Dendreon, Algeta/Bayer, Bristol Myers Squibb, EMD Serono, Astellas Pharma  Disclaimer:   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast expressed their own opinions, experience, and conclusions. Guest statements on the 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.       

Toni Choueiri looks back at the year in kidney cancer.

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

In 2015, when he was 48, Chuck was diagnosed with advanced (stage 4) renal cell carcinoma or kidney cancer. He had a cold and noticed blood in his urine. He credits the thoroughness of his primary care physician for immediately sending him for diagnostic tests where they discovered a massive tumor two days later. He is married to his high school sweetheart Liz, and they have 4 daughters He has undergone multiple surgeries and has participated in numerous clinical trials. He works as the vice president of business operations at the National Fire Protection Agency and is a life-long Boston sports fan and die-hard Boston College Eagles fan.  See omnystudio.com/listener for privacy information.

Toni Choueiri describes the KN564 study in detail.

Dr. Neeraj Agarwal, director of the Genitourinary Oncology Program at the University of Utah Huntsman Cancer Institute and associate editor of ASCO Daily News, highlights key abstracts in GU oncology featured at the 2021 ASCO Annual Meeting.   Transcript: ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Neeraj Agarwal, a medical oncologist and director of the Genitourinary Oncology Program at the University of Utah Huntsman Cancer Institute. He joins me to discuss key abstracts in the GU field featured at the 2021 ASCO Annual Meeting.   Dr. Agarwal has served in a consulting or advisory role for AstraZeneca, Bristol Myers Squibb, Exelixis, and Merck, among other organizations. He is a co-author of a study, Abstract 5073, that will be discussed in this episode. Dr. Agarwal's full disclosures and those relating to all episodes of the podcast are available on our transcripts at asco.org/podcasts.   Dr. Agarwal, it's great to have you on the podcast again.   Dr. Neeraj Agarwal: It's my pleasure, and an honor. Thank you very much for having me.   ASCO Daily News: Dr. Agarwal, let's start with some exciting news in the field of kidney cancer. LBA5 addressed the Keynote 564 trial, which evaluated pembrolizumab versus placebo as adjuvant therapy for patients with renal cell carcinoma. This study reported stunning results. What can you tell us about this trial?   Dr. Neeraj Agarwal: These are very important results from the Abstract LBA5, which is being presented by Dr. Toni Choueiri, from Dana Farber Cancer Institute, and colleagues on interim results from the KEYNOTE-564 trial, which showed that adjuvant therapy with pembrolizumab after complete resection of intermediate high, high-risk, localized or oligometastatic renal cell carcinoma improves survival outcomes.   So, let me give you a background first. Partial and radical nephrectomy is considered standard of care for treatment of men or women with localized renal cell carcinoma. However, approximately half of these patients eventually recur. In addition, many patients with limited metastatic disease undergo surgical resection.   Currently, there is no standard of care systemic therapy available for these patients. So, the KEYNOTE-564 study is a phase III trial evaluating pembrolizumab versus placebo--which is a standard of care, by the way, for these patients as adjuvant therapy for patients with clear cell renal cell carcinoma with intermediate high risk, high-risk, or those with metastatic disease who have undergone complete resection of metastatic disease.   Primary endpoint was disease-free survival for investigator assessment, in intent-to-treat population. Overall survival was a key secondary endpoint. In this study, a total of 994 patients were randomized, one to one, to pembrolizumab or placebo. At the time of data cutoff, median follow up was 2 years. There were no patients remaining on the study treatment.   If you look at the baseline characteristics, they were evenly balanced between the two arms. At the first, prespecified interim analysis, the primary endpoint of disease-free survival was met, though the median values were not reached for both arms. Pembrolizumab was associated with a significantly longer disease-free survival than placebo, with a hazard ratio of 0.68 and a one-sided p-value of 0.001, which translates into 32% reduction in risk of recurrence of disease or death with adjuvant pembrolizumab.   The 2- year rate of disease-free survival was 77.3% with pembrolizumab, as compared to 68% of the placebo. Overall, disease-free survival benefit was consistent across subgroups. Median overall survival was not reached for either groups, and the estimated 24 months survival rate was high in both groups at 96% and 93.5% with pembrolizumab and placebo, respectively. And really, there were no new safety signals seen with pembrolizumab.   So, I'd like to summarize these important results by saying that KEYNOTE-564 is the first positive, phase III study with a checkpoint inhibitor for patients with renal cell carcinoma, which has been surgically resected completely. And for them, right now, there is no real standard of care after the surgical resection. So, in my view, these results support pembrolizumab as a potential new standard of care for these patients who present to us after a complete surgical resection of their renal cell carcinoma.   ASCO Daily News: Excellent. Thank you for sharing those practice-changing results. There's another late-breaking abstract that people are excited about. That's LBA4 and the VISION phase III study, which used a novel PSMA-targeting agent for patients with metastatic, castration-resistant prostate cancer. What can you tell us about the VISION trial?   Dr. Neeraj Agarwal: The VISION trial was reported by Dr. Mike Morris, from Memorial Sloan Kettering Hospital, and colleagues from across the planet. And this trial investigated the use of the Lutetium PSMA-617 in patients with metastatic, castration-resistant prostate cancer. As a background, Lutetium PSMA 617 is a targeted, radioligand therapy which delivers beta particle radiation to PSMA-expressing prostate cancer cells and surrounding microenvironment.   So, VISION was a randomized, open-label, phase III study, which evaluated Lutetium PSMA-617 in men with PSMA-positive, metastatic, castration-resistant prostate cancer, who had received prior treatment with the next generation androgen signaling inhibitors, such as enzalutamide and one or two taxane therapy regimens. Primary endpoint was radiographic progression-free survival, as well as there was another primary endpoint.   So, there were two primary endpoints--radiographic progression free survival, and overall survival. A total of 831 patients--so this is a large study--where 831 patients were randomly assigned in 2 to 1 fashion to receive Lutetium PSMA-617, plus standard of care, or standard of care therapy alone. I would like to point this out, that standard of care therapy was to be determined by the investigator, but excluded cytotoxic chemotherapy and radium 223.   The median study follow up was 20.9 months at the time of data cutoff. The baseline characteristics were well balanced between treatment arms. Lutetium PSMA-617 plus standard of care therapy significantly improved radiographic progression free survival and overall survival, versus standard of care therapy alone. The median radiographic progression free survival with lutetium PSMA-617 plus standard of care was 8.7 months, as compared to 3.4 months with standard of care alone, with a hazard ratio of 0.40, favoring the lutetium PSMA- 617.   The median overall survival with lutetium PSMA-617 plus standard of care was 15.3 months, as compared to 11.3 months with standard of care, with a hazard ratio of 0.62. These results basically translate into an absolute 4-month improvement in median overall survival, and a 38% reduction in risk of death, with PSMA-617 plus standard of care over the standard of care. I would like to point out that key secondary endpoints of objective response rates, disease control rate, and time to subsequent or first symptomatic skeletal event were statistically significant, and favored lutetium PSMA 617.   Overall, if you look at the treatment emergent adverse events, they were higher in the lutetium PSMA arm, at 52.7%, compared to those on the standard of care arm, which was 38%. And these were high grade treatment emergent adverse events. So, I'd like to conclude by saying that lutetium PSMA-617 plus standard of care treatment was a well-tolerated regimen that improved radiographic progression-free survival, and overall survival, as compared with standard of care therapy alone, in men with PSMA-positive, metastatic, castration-resistant prostate cancer, after prior treatment with novel hormonal receptor signaling inhibitors, such as enzalutamide or abiraterone and taxane chemotherapy.   Once approved by regulatory bodies, I am looking forward to using this agent in my clinic for our patients with metastatic, castration-resistant prostate cancer who have had disease progression on prior therapy with normal hormonal therapy and taxane chemotherapy. So, this is indeed a great news for our patients.   ASCO Daily News: Absolutely. Well, I'd like to ask you about adolescents and young adults with cancer. As you know, AYA patients navigate a lot of challenges in their cancer experience. Can you tell us about any studies that address this patient population?   Dr. Neeraj Agarwal: Indeed. There was an abstract--Abstract 5006, which is being presented by Dr. Hellesnes and colleagues from University Hospital of North Norway. The study team investigated non-testicular cancer mortality in relation to testicular cancer treatment in a large population-based cohort. Overall, 5,700 men, diagnosed with testicular cancer from 1980 to 2009, were included and identified from the cancer registry of Norway.   Clinical parameters and treatment data were abstracted from the medical records and linked with the Norwegian cause of death registry. During a median follow up of 18.7 years--it is a long follow up, by the way--in total, 665--or 12% of men--were registered with non-testicular cancer deaths. The overall excess non-testicular cancer mortality was 23% in men with a history of testicular cancer, as compared with the general population.   So, I'd like to repeat. There was an overall excessive non-testicular cancer mortality in men with a history of testicular cancer compared to the general population--by 23%. That's the first message I'm giving here. Second, there was an increased risk observed with platinum-based chemotherapy and radiation therapy, but not after surgery. So, I thought it was very interesting that there was an increased risk of non-testicular cancer mortality seen after platinum-based chemotherapy and/or radiation therapy, but not after surgery given the context of testicular cancer.   The standardized mortality ratios increased significantly, with increasing follow up time of 10 or more years. The most important cause of death wasn't second cancer. Treatment with platinum-based chemotherapy was associated with a significant 1.69 to 6.78-fold increased standardized mortality ratio for cancers of the oral cavity, pharynx, esophagus, lungs, bladder, and leukemia. After radiation therapy given for testicular cancer, there was an increased--significantly increased--and we are talking about 3.02 to 4.91-fold increase--the standardized mortality ratio for cancers of oral cavity, pharynx, stomach, liver, pancreas, and bladder. Even non-cancer mortality was also increased by 15% after both platinum-based chemotherapy and radiation therapy.   I would like to highlight that there was an excess in suicides after platinum-based chemotherapy with a standardized mortality ratio of 1.65. So long term, overall cardiovascular mortality--and I found it interesting, because it is going against the dogma here--that long term, overall cardiovascular mortality was not increased with either chemotherapy or radiation therapy. So, I'd like to conclude--regarding this abstract--by saying that testicular cancer treatment with platinum-based chemotherapy or radiation therapy was associated with significantly increased long term, non-testicular cancer mortality, with non-testicular second cancer being the most important cause of death in these patients.   So, in my view, these results have important implications on patient counseling, selection of treatment for testicular cancer, and, very importantly, long term follow up of our young patients with testicular cancer after they are apparently cured of testicular cancer with platinum-based chemotherapy and/or radiation therapy. And usually we stop following them, in most cases, after 5 years. And how these results are going to impact the decision making regarding their long-term follow up. So, I think this study brings up a very important issue from those perspectives.   ASCO Daily News: Absolutely. Dr. Agarwal, I'd like to get your thoughts on Abstract 5004. That addresses PSA screening for African American men. What can you tell us about this study?   Dr. Neeraj Agarwal: So, this abstract, which is Abstract 5004, presented by Dr. Edmund Qiao and colleagues, examined the association of intensity of PSA screening with the disease severity of prostate cancer at the time of diagnosis, as well as prostate cancer-specific mortality in African American men younger than 55 years of age. So, I'd like to highlight two things, which this study is presenting.   Number one, the screening intensity in African American men, and second, how it is affecting the time of diagnosis, the type of diagnosis--meaning is it a high grade or metastatic prostate cancer--and most importantly, is it affecting prostate cancer-specific mortality in African American men? So, this was a retrospective review of Veterans Health Administration records of African American men, aged 40 to 55 years, who were diagnosed with prostate cancer between the years of 2004 to 2017.   The screening intensity was defined as percentage of years screened within the pre-diagnostic observation period. The cohort included 4,654 African American men, with a mean age of 51.8 years--so quite a younger population. A median pre-diagnostic observation period of 5 years, and a median follow up of 7 years. And these are pretty decent, long median follow ups of 7 years.   So, in this large national cohort, African American men aged 40 to 55 years, increased intensity of PSA screening was significantly associated with decreased risk of metastatic prostate cancer, or high Gleason Score localized prostate cancer, and more importantly, prostate cancer-specific mortality. So, in my view, these results have important implications on how to screen African American men in the age group of 40- to 55-year-olds.   Obviously, we don't screen for prostate cancer. And please note that these are the men who are more likely than others to present and die of aggressive prostate cancer. And even more importantly, these men are underrepresented in PSA screening studies. So, I think a lot of good lessons coming from this study.   ASCO Daily News: Indeed. Well, racial disparities are also addressed in a Medicare database study captured in Abstract 5073. The study set out to evaluate the real-world utilization of advanced therapies over time, and to provide data on utilization patterns among racial minorities that are often underrepresented in clinical trials. Can you tell us more about this study?   Dr Neeraj Agarwal:  Yes. Indeed. These data, presented by Dr. Steve Freedland from Cedars-Sinai, and colleagues, which highlighted a critical issue of unacceptably high number of patients with metastatic castration-sensitive prostate cancer not receiving standard of care, life-prolonging therapy in the United States. In this study, which I also had the opportunity to co-author, the investigators evaluated real-world utilization of systemic therapies backed by level 1 evidence from large randomized phase III trials, which showed treatment intensification with docetaxel, or novel hormonal therapies, such as abiraterone, dramatically improved overall survival in men with metastatic castration-sensitive prostate cancer.   In addition, the study team also evaluated the receipt of these therapies by racial minorities who are usually underrepresented in these clinical trials. So, this was a retrospective study of a Medicare database, which covered the time period between January 2009 and December 2018. Adult men with new diagnosis of metastatic prostate cancer were included. The first line treatments were grouped by prostate cancer specific drugs prescribed within 30 days prior to, and 120 days after the index date, which was the date of diagnosis of metastatic disease.   Remarkably, a total of more than 35,000 patients with metastatic castration-sensitive prostate cancer were included in the study. These comprise 12% patients who are African American, 5.3% patients [who were] Hispanic men, and 78.5% men who were white. So, the study had a good representation of racial minorities.  The results were startling to me.   Starting in the year 2015 or ‘16, when docetaxel was already approved after showing dramatic improvement in overall survival, which was soon followed by similar results with abiraterone, within a couple of years showing similar overall survival benefit--less than one third patients with metastatic castration-sensitive prostate cancer received these therapies from 2015 until 2018. The treatment intensification, which is the terminology used for combination of androgen deprivation therapy with docetaxel or novel hormonal therapy such as abiraterone, enzalutamide, and apalutamide--so treatment intensification was even lower for Black patients than white patients.   So, to summarize, in this large and nationally representative patient population with diagnosis of metastatic castration-sensitive prostate cancer, less than one third patients received standard of care treatment intensification, even in the year 2018. More importantly, the data showed even less frequent use of treatment intensification in Black patients versus white patients. A similar study, by my colleague, Dr. Umang Swami from Huntsman Cancer Institute, in the Abstract 5072, also showed that despite level 1 evidence demonstrating improved survival with intensified regimens with ADT plus docetaxel or normal hormonal therapy, such as, as I said, abiraterone, enzalutamide, apalutamide--frequent intensification was underutilized in men with metastatic castration-sensitive prostate cancer, in more than 4,000 patients studied.   And importantly, these patients were included from the claims data from commercially insured--I want to repeat--commercial insured and Medicare Advantage populations. So, these patients you would expect to have good financial coverage for their treatment. And even then, less than one third patients were receiving this standard of care, intensified treatments backed by level one evidence from phase III trials. Less than one third patients were receiving this therapy.   Even in patients with visceral metastasis--which we know is the most aggressive form of prostate cancer--there was a similarly low level of treatment intensification. So, I think these data are very important for us to know. And there are important steps for us to take down the line. We do not know why this is happening.   Why are our patients are not being offered standard of care, life prolonging therapies for castration-sensitive disease? Is it an access problem? Is it a problem with education, awareness? We do not know. So, I think a lot of works needs to be done in this direction.   ASCO Daily News: Absolutely. These data are very, very concerning. Dr. Agarwal, thank you very much for sharing your incredible insight with us today, and highlighting these very impactful studies in the GU field.   Dr. Neeraj Agarwal: Thank you very much for having me.   ASCO Daily News: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe, wherever you get your podcasts.     Disclosures: Dr. Neeraj Agarwal  Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Exelixis, Merck, Novartis, Eisai,   Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Inst.): Bayer Your Institution , Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen,   AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas  Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.      

Robert Figlin, MD, Steven Spielberg Family Chair in Hematology-Oncology, Cedars-Sinai Medical Center and Toni Choueiri, MD, Director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute, discuss clinical progress in renal cell carcinoma (RCC)

Details of the study......

Co-hosts Charu Aggarwal and Jack West are joined by Dr. Toni Choueiri to discuss the role of twitter for education, mentorship and a platform for sharing credible information.

The group attempts to put the data into context with the other available combinations.

Dr. Toni Choueiri discusses the results of this study, which appears to show a survival signal, but it is difficult to interpret.

Professor Tom Powles, Dr. Brian Rini and Dr. Toni Choueiri discuss the evolving landscape in Boston, and meetings such as ASCO and ESMO in 2020.

Toni Choueiri, MD, kidney cancer specialist at Dana-Farber Cancer Institute, discusses surgical considerations and multidisciplinary care for localized kidney cancer, adjuvant therapies largely falling short of expectations, and the plethora of frontline therapies available in metastatic disease.

Robert Figlin, MD, Steven Spielberg Family Chair in Hematology-Oncology, Cedars-Sinai Medical Center and Toni Choueiri, MD, Director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute, discuss Keytruda's approval in renal cell carcinoma (RCC).

Lenny has been fighting kidney cancer in one form or another since 2008. After doctors discovered a tumor in his kidney ten years ago, Lenny underwent several surgeries to remove tumor growths and eventually had his entire kidney removed. Unfortunately, Lenny's disease came back in 2013, and this time surgery was no longer an option. He now had an inoperable form of the disease that had spread to other parts of his body as well.Lenny started on clinical trial of a targeted drug that helped to shrink his tumor dramatically. Lenny was also feeling good and experienced minimal side effects while on the trial.When his disease returned in 2015, Lenny had additional treatment options at Dana-Farber. He started on a new form of therapy called immunotherapy. Immunotherapy harnesses the body's own immune system to recognize and destroy cancer cells, much the same way our immune system seeks out a virus or infection. Lenny's tumors have not grown since he has been on this new medication. While every day is challenge in some ways for Lenny, he maintains an upbeat and positive outlook. He calls Dr. Choueiri and his treatment team the best thing that ever happened to him.Dr. Choueiri the lead investigator of multiple national and international phase one, two and three trials in GU cancers.Dr. Choueiri is interested in developing novel therapies and biomarkers in GU malignancies, including kidney cancer. His research also focuses on epidemiology, diagnosis and treatment outcomes of GU cancers using large scale approaches such as meta-analyses from available published trials or national databases.

In 2010, Bobbi had a tumor in her kidney, and had her kidney removed. She continued to see the doctor for regular check-ups and in March 2013 she learned she had metastatic kidney cancer. She was immediately treated with immunotherapy and she has continued to respond positively to treatment. She had to start a second drug recently when her doctor discovered an enlarged lymph node. Bobbi is retired from the HR department of the Department of Corrections, she worked there for 25 years. She has been married to her husband, Buddy for 51 years. They have an adult son and daughter, and have a granddaughter who is 5. Dr. Chouieri makes her smile. She says he is straightforward and patient and always answers all her questions. She said it is easy to see why his nickname is “Dr. Wonderful.”