Drs Sumanta Pal and Brian Rini discuss front-line treatment of renal cell carcinoma.

Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968736). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals.

Resources

Bevacizumab Plus Interferon-alpha Versus Interferon-alpha Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Results of Overall Survival for CALGB 90206 https://ascopubs.org/doi/10.1200/jco.2009.27.18_suppl.lba5019

An updated table of the front-line IO combination RCC studies that have shown an OS advantage https://twitter.com/brian_rini/status/1309609380585844736/photo/1

Targeting PD-1 or PD-L1 in Metastatic Kidney Cancer: Combination Therapy in the First-Line Setting https://aacrjournals.org/clincancerres/article/26/9/2087/83102/Targeting-PD-1-or-PD-L1-in-Metastatic-Kidney

Conditional Survival and Long-term Efficacy With Nivolumab Plus Ipilimumab Versus Sunitinib in Patients With Advanced Renal Cell Carcinoma https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34180

International Metastatic Renal Cell Carcinoma Database Consortium Criteria https://www.uptodate.com/contents/image?imageKey=ONC%2F116130&topicKey=ONC%2F2984&source=see_link

Molecular Correlates Differentiate Response to Atezolizumab (atezo) + Bevacizumab (bev) vs Sunitinib (sun): Results From a Phase III Study (IMmotion151) in Untreated Metastatic Renal Cell Carcinoma (mRCC) https://cslide.ctimeetingtech.com/esmo2018/attendee/confcal/presentation/list?q=LBA31

Nivolumab Versus Everolimus in Patients With Advanced Renal Cell Carcinoma: Updated Results With Long-term Follow-up of the Randomized, Open-Label, Phase 3 CheckMate 025 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415096/pdf/nihms-1732721.pdf

Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma https://www.nejm.org/doi/10.1056/NEJMoa2035716

The Uromigos Debate: Treatment of Favorable Risk Renal Cancer https://anchor.fm/the-uromigos/episodes/Episode-67-The-Third-Uromigos-Debate---fPD1VEGF-vs-PD1CTLA4-for-front-line-renal-cancer-emjpji

Health-Related Quality-of-Life Outcomes in Patients With Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab or Everolimus Versus Sunitinib (CLEAR): A Randomised, Phase 3 Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00212-1/fulltext

Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313) https://clinicaltrials.gov/ct2/show/NCT03937219

A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012) https://clinicaltrials.gov/ct2/show/NCT04736706

Twitter poll questions:

• What magnitude of benefit is required to adopt triplets? OS https://mobile.twitter.com/brian_rini/status/1508450496104783877
• What magnitude of absolute PFS benefit vs doublets is required to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508450910506295305
• What would be the most convincing endpoint to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508451622564909057

Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436590/

OPtimal Treatment by Invoking biologic Clusters in Renal Cell Carcinoma (OPTIC RCC) https://www.kcameetings.org/wp-content/uploads/2021/12/IKCSNA21_TIP8_Chen.pdf

Drs Sumanta Pal and Tian Zhang review the state of the data on adjuvant treatment with immunotherapy for patients with renal cell carcinoma, including where current clinical trials stand.

Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968737). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals.

Resources

Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study https://clinicaltrials.gov/ct2/show/NCT03793166

The Role of Targeted Therapy in the Management of High-Risk Resected Kidney Cancer: What Have We Learned and How Will It Inform Future Adjuvant Trials https://journals.lww.com/journalppo/Abstract/2020/09000/The_Role_of_Targeted_Therapy_in_the_Management_of.3.aspx

Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy https://www.nejm.org/doi/10.1056/NEJMoa1611406

Sutent (sunitinib) prescribing information https://labeling.pfizer.com/showlabeling.aspx?id=607

Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma (KEYNOTE-564) https://www.nejm.org/doi/full/10.1056/NEJMoa2106391

RAMPART: A Phase III Multi-arm Multi-stage Trial of Adjuvant Checkpoint Inhibitors in Patients With Resected Primary Renal Cell Carcinoma (RCC) at High or Intermediate Risk of Relapse https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520913/

A Study of Atezolizumab as Adjuvant Therapy in Participants With Renal Cell Carcinoma (RCC) at High Risk of Developing Metastasis Following Nephrectomy (IMmotion010) https://clinicaltrials.gov/ct2/show/NCT03024996

A Comparison of Sunitinib with Cabozantinib, Crizotinib, and Savolitinib for Treatment of Advanced Papillary Renal Cell Carcinoma: a Randomised, Open-Label, Phase 2 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687736/

A Study Comparing Nivolumab, Nivolumab in Combination With Ipilimumab and Placebo in Participants With Localized Kidney Cancer Who Underwent Surgery to Remove Part of a Kidney (CheckMate 914) https://clinicaltrials.gov/ct2/show/NCT03138512

PROSPER: Phase III RandOmized Study Comparing PERioperative nivolumab versus observation in patients with renal cell carcinoma (RCC) undergoing nephrectomy (ECOG-ACRIN EA8143). https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.TPS4596

Pembrolizumab as Post Nephrectomy Adjuvant Therapy for Patients With Renal Cell Carcinoma: Results From 30-Month Follow-up of KEYNOTE-564 https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.6_suppl.290

Leibovich RCC Model: Prediction of Progression After Radical Nephrectomy for patients With Clear Cell Renal Cell Carcinoma https://cancernomograms.com/nomograms/972

Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell Carcinoma Patients without Overt Metastases: Results From ASSURE, ECOG 2805 https://aacrjournals.org/clincancerres/article/21/18/4048/117759/Effects-of-Adjuvant-Sorafenib-and-Sunitinib-on

Drs Sumanta Pal and Mehmet Asim Bilen discuss the complexities of treating patients with non–clear cell renal carcinoma, the nuances of rare subtypes, and when to use chemotherapy vs immunotherapy.

Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968741). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals.

Resources

Renal Cell Carcinoma https://emedicine.medscape.com/article/281340-overview

Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology https://pubmed.ncbi.nlm.nih.gov/34991070/

PAPMET Trial: Testing Cabozantinib, Crizotinib, Savolitinib and Sunitinib in Kidney Cancer Which Has Progressed https://clinicaltrials.gov/ct2/show/NCT02761057

Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non–Clear-Cell Renal Cell Carcinoma and Genomic Correlates https://ascopubs.org/doi/10.1200/JCO.21.01944

Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605393/

Cabozantinib Plus Nivolumab Phase I Expansion Study in Patients With Metastatic Urothelial Carcinoma Refractory to Immune Checkpoint Inhibitor Therapy https://aacrjournals.org/clincancerres/article/28/7/1353/682207/Cabozantinib-plus-Nivolumab-Phase-I-Expansion

Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study https://ascopubs.org/doi/10.1200/JCO.21.00939

A Single-Arm, Multicenter, Phase 2 Study of Lenvatinib Plus Everolimus in Patients With Advanced Non–Clear Cell Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/33867192/

ESMO 2022 https://www.esmo.org/meetings/esmo-immuno-oncology-congress-2022/abstracts

Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma. The SAVOIR Phase 3 Randomized Clinical Trial https://jamanetwork.com/journals/jamaoncology/fullarticle/2766797

SAMETA: An Open-Label, Three-Arm, Multicenter, Phase III Study of Savolitinib + Durvalumab Versus Sunitinib and Durvalumab Monotherapy in Patients With MET-Driven, Unresectable, Locally Advanced/Metastatic Papillary Renal Cell Carcinoma (PRCC). https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.TPS4601

A Phase II Trial of Doxorubicin and Gemcitabine in Renal Cell Carcinoma With Sarcomatoid Features: ECOG 8802 https://pubmed.ncbi.nlm.nih.gov/21298497/

A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 9ER) https://clinicaltrials.gov/ct2/show/NCT03141177

Drs Sumanta Pal and Jennifer Wargo discuss how the gut microbiome impacts response to cancer therapy in patients with renal cell carcinoma.

Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968742). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals.

Resources

Gut Microbiome Modulates Response to Anti-PD-1 Immunotherapy in Melanoma Patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827966/

The Microbiome in Cancer Immunotherapy: Diagnostic Tools and Therapeutic Strategies https://pubmed.ncbi.nlm.nih.gov/29567708/

Commensal Bifidobacterium Promotes Antitumor Immunity and Facilitates Anti-PD-L1 Efficacy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873287/

Anticancer Immunotherapy by CTLA-4 Blockade Relies on the Gut Microbiota https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721659/

Gut Microbiome Influences Efficacy of PD-1-Based Immunotherapy Against Epithelial Tumors https://pubmed.ncbi.nlm.nih.gov/29097494/

Dietary Fiber and Probiotics Influence the Gut Microbiome and Melanoma Immunotherapy Response https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970537/

Fiber in Diet Linked to Cancer Immunotherapy Response https://www.nih.gov/news-events/nih-research-matters/fiber-diet-linked-cancer-immunotherapy-response

Fecal Microbiota Transplant Promotes Response in Immunotherapy-Refractory Melanoma Patients https://www.science.org/doi/10.1126/science.abb5920

Fecal Microbiota Transplant Overcomes Resistance to Anti-PD-1 Therapy in Melanoma Patients https://pubmed.ncbi.nlm.nih.gov/33542131/

Fecal Microbiota for Transplantation: Safety Alert - Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms https://www.fda.gov/safety/medical-product-safety-information/fecal-microbiota-transplantation-safety-alert-risk-serious-adverse-events-likely-due-transmission

Fecal Microbiota Transplantation Followed by Anti–PD-1 Treatment in Patients With Advanced Melanoma https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.9533

Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma https://clinicaltrials.gov/ct2/show/NCT04940299

Nivolumab plus Ipilimumab With or Without Live Bacterial Supplementation in Metastatic Renal Cell Carcinoma: A Randomized Phase 1 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018425/

Drs Sumanta Pal and Rana McKay discuss the use of biomarkers in treating patients with renal cell carcinoma to identify whose disease will recur and who will respond to therapy.

Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968743). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals.

Resources

Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma https://ascopubs.org/doi/10.1200/JCO.22.00219

The Detection of EpCAM+ and EpCAM­– Circulating Tumor Cells https://www.nature.com/articles/srep12270

Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768333/

ctDNA Guiding Adjuvant Immunotherapy in Urothelial Carcinoma https://www.nature.com/articles/s41586-021-03642-9

Clinical Activity and Molecular Correlates of Response to Atezolizumab Alone or in Combination With Bevacizumab Versus Sunitinib in Renal Cell Carcinoma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721896/

Atezolizumab Plus Bevacizumab Versus Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (IMmotion151): A Multicentre, Open-Label, Phase 3, Randomised Controlled Trial https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(19)30723-8

Nivolumab Plus Ipilimumab Versus Sunitinib in Advanced Renal-Cell Carcinoma https://www.nejm.org/doi/full/10.1056/nejmoa1712126

Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study https://clinicaltrials.gov/ct2/show/NCT05361720

Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313) https://clinicaltrials.gov/ct2/show/NCT03937219

Single-Cell RNA Sequencing of Human Kidney https://www.nature.com/articles/s41597-019-0351-8

Progressive Immune Dysfunction With Advancing Disease Stage in Renal Cell Carcinoma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138872/

Drs Sumanta Pal and Martin Voss discuss second-line treatment of renal cell carcinoma, including current studies and agents used in the refractory setting.

Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968745). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals.

Resources

Renal Cell Carcinoma Treatment & Management https://emedicine.medscape.com/article/281340-treatment

Comparative Effectiveness of Axitinib Versus Sorafenib in Advanced Renal Cell Carcinoma (AXIS): A Randomised Phase 3 Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61613-9/fulltext

Cabozantinib Versus Everolimus in Advanced Renal-Cell Carcinoma https://www.nejm.org/doi/full/10.1056/NEJMoa1510016

CANTATA: Primary Analysis of a Global, Randomized, Placebo (Pbo)-Controlled, Double-Blind Trial of Telaglenastat (CB-839) + Cabozantinib Versus Pbo + Cabozantinib in Advanced/Metastatic Renal Cell Carcinoma (mRCC) Patients (pts) Who Progressed on Immune Checkpoint Inhibitor (ICI) or Anti-Angiogenic Therapies. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.4501

FDA Approves Tivozanib for Relapsed or Refractory Advanced Renal Cell Carcinoma https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tivozanib-relapsed-or-refractory-advanced-renal-cell-carcinoma

Tivozanib Versus Sorafenib in Patients With Advanced Renal Cell Carcinoma (TIVO-3): A Phase 3, Multicentre, Randomised, Controlled, Open-Label Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30735-1/fulltext

Lenvatinib, Everolimus, and the Combination in Patients With Metastatic Renal Cell Carcinoma: A Randomised, Phase 2, Open-Label, Multicentre Trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00290-9/fulltext

A Study of Atezolizumab in Combination With Cabozantinib Compared to Cabozantinib Alone in Participants With Advanced Renal Cell Carcinoma After Immune Checkpoint Inhibitor Treatment (CONTACT-03) https://clinicaltrials.gov/ct2/show/NCT04338269

TiNivo: Safety and Efficacy of Tivozanib-Nivolumab Combination Therapy in Patients With Metastatic Renal Cell Carcinoma https://linkinghub.elsevier.com/retrieve/pii/S0923-7534(20)42472-X

Kidney Cancer Research Summit https://kcrs.kidneycan.org/

Drs Sumanta Pal and Scott Haake discuss the biology of kidney cancer and how to incorporate tissue biomarkers into prospective studies on renal cell carcinoma.

Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984237). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals.

Resources

W. Kimryn Rathmell, MD, PhD, MMHC https://www.vumc.org/viiii/person/w-kimryn-rathmell-md-phd-mmhc

Novel Emerging Biomarkers to Immunotherapy in Kidney Cancer https://pubmed.ncbi.nlm.nih.gov/34868351/

PD1 and PD-L1 Inhibitors for the Treatment of Kidney Cancer: The Role of PD-L1 Assay https://pubmed.ncbi.nlm.nih.gov/32208115/

Oncogene-Specific Differences in Tumor Mutational Burden, PD-L1 Expression, and Outcomes From Immunotherapy in Non-Small Cell Lung Cancer https://pubmed.ncbi.nlm.nih.gov/34376553/

Multiomics in Primary and Metastatic Breast Tumors From the AURORA US Network Finds Microenvironment and Epigenetic Drivers of Metastasis https://pubmed.ncbi.nlm.nih.gov/36585450/

Avelumab Plus Axitinib Versus Sunitinib in Advanced Renal Cell Carcinoma: Biomarker Analysis of the Phase 3 JAVELIN Renal 101 Trial https://pubmed.ncbi.nlm.nih.gov/32895571/

Clinical Activity and Molecular Correlates of Response to Atezolizumab Alone or in Combination With Bevacizumab Versus Sunitinib in Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/29867230/

Atezolizumab Plus Bevacizumab Versus Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (IMmotion151): A Multicentre, Open-Label, Phase 3, Randomised Controlled Trial https://pubmed.ncbi.nlm.nih.gov/31079938/

Insights Into the Genetic Basis of the Renal Cell Carcinomas From the Cancer Genome Atlas https://pubmed.ncbi.nlm.nih.gov/27330105/

Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study https://clinicaltrials.gov/ct2/show/NCT05361720

Drs Sumanta Pal and David A. Braun discuss the role of single-cell sequencing as a biomarker in renal cell carcinoma, how it is evolving, and how it might apply in other domains.

Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984238). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals.

Resources

Single-Cell RNA Sequencing Technologies and Applications: A Brief Overview https://pubmed.ncbi.nlm.nih.gov/35352511/

Progressive Immune Dysfunction With Advancing Disease Stage in Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/33711273/

Immune Checkpoint Inhibitors in Non-Conventional Histologies of Renal-Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/36758960/

Prevalence and Landscape of Actionable Genomic Alterations in Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/34261695/

Molecular Profiling in Early ER+ Breast Cancer to Aid Systemic Therapy Decisions https://pubmed.ncbi.nlm.nih.gov/36862337/

Dysbiosis of a Microbiota-Immune Metasystem in Critical Illness Is Associated With Nosocomial Infections https://pubmed.ncbi.nlm.nih.gov/36894652/

A Single-Cell Atlas Reveals Shared and Distinct Immune Responses and Metabolic Profiles in SARS-CoV-2 and HIV-1 Infections https://pubmed.ncbi.nlm.nih.gov/36992700/

Revealing the Vectors of Cellular Identity With Single-Cell Genomics https://pubmed.ncbi.nlm.nih.gov/27824854/

Nivolumab Versus Everolimus in Patients With Advanced Renal Cell Carcinoma: Updated Results With Long-term Follow-up of the Randomized, Open-Label, Phase 3 CheckMate 025 Trial https://pubmed.ncbi.nlm.nih.gov/32673417/