Addressing Current Questions Related to the Management of Renal Cell Carcinoma — Symposium Video Proceedings

Faculty

TARGET AUDIENCE
This program is intended for medical and radiation oncologists, urologists and other healthcare providers involved in the treatment of renal cell carcinoma.

LEARNING OBJECTIVES

• Evaluate recently presented data with adjuvant anti-PD-1/PD-L1 antibody therapy for patients with RCC at high risk for recurrence after nephrectomy, and consider the current role of this treatment strategy.
• Appraise available clinical trial data evaluating anti-PD-1/PD-L1 antibody/multikinase inhibitor combinations for previously untreated metastatic RCC (mRCC), and counsel patients regarding the risks and benefits of these novel regimens.
• Review the biological rationale underlying the investigation of anti-PD-1/anti-CTLA-4 combination therapy as first-line treatment for patients with mRCC, and appreciate long-term research findings documenting the effectiveness of this approach.
• Assess recently presented clinical trial results with anti-PD-1/PD-L1 antibodies administered as a subcutaneous injection for patients with mRCC, and reflect on the potential benefits of this therapeutic strategy.
• Understand the biological rationale for exploiting HIF-2α in patients with von Hippel-Lindau-associated and sporadic RCC, and consider the current role of available inhibitors.
• Develop a rational therapeutic approach to the sequencing of systemic therapies for patients with advanced RCC that progresses on first-line treatment, incorporating multikinase inhibitors, HIF-2α inhibitors, immunotherapeutic agents and other strategies.
• Appreciate published research findings evaluating the use of available and investigational agents for patients with non-clear cell RCC, and consider the applicability of these strategies in clinical care.
• Recall available and emerging data with other novel and investigational agents and strategies in testing for RCC, and as applicable, refer eligible patients for clinical trial participation.

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Video Program: This CME activity consists of an video component.
CME credit is no longer available for this issue

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FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Thomas E Hutson, DO, PharmD, PhD
Director
UMC Cancer Center
Division Chief, Hematology and Medical Oncology
Professor of Medicine
CH Endowed Chair
Texas Tech University Health Sciences Center School of Medicine
Lubbock, Texas

Advisory Committees, Consulting Agreements, Contracted Research and Speakers Bureaus: Astellas, AstraZeneca Pharmaceuticals LP, EMD Serono Inc, Exelixis Inc, Merck, Pfizer Inc, Seagen Inc.

Rana R McKay, MD
Professor of Medicine and Urology
Associate Director, Clinical Research
Co-Lead, Genitourinary Program
Moores Cancer Center
University of California San Diego
San Diego, California

Advisor/Consultant: Ambrx, Arcus Biosciences, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Blue Earth Diagnostics, Bristol Myers Squibb, Calithera Biosciences, Caris Life Sciences, Daiichi Sankyo Inc, Dendreon Pharmaceuticals Inc, Exelixis Inc, Johnson & Johnson Pharmaceuticals, Lilly, Merck, Myovant Sciences, Neomorph, Novartis, Pfizer Inc, Sanofi, Seagen Inc, Sorrento Therapeutics, Telix Pharmaceuticals Limited, Tempus; Institutional Research Funding: ArteraAI, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Exelixis Inc, Oncternal Therapeutics, Tempus.

Tian Zhang, MD, MHS
Associate Professor
Director of Clinical Research
Division of Hematology and Oncology
Department of Internal Medicine
UT Southwestern Medical Center
Associate Director for Clinical Research
Simmons Comprehensive Cancer Center
Dallas, Texas

Advisory Committees: Amgen Inc, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Dendreon Pharmaceuticals Inc, Eisai Inc, EMD Serono Inc, Exelixis Inc, Gilead Sciences Inc, Janssen Biotech Inc, Lilly, Merck, Novartis, Pfizer Inc, Sanofi; Consulting Agreements: Aptitude Health, DAVA Oncology, Pfizer Inc, Vaniam Group; Contracted Research: ALX Oncology, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Exelixis Inc, Janssen Biotech Inc, Janux Therapeutics, Lilly, Merck, OncoC4, Pfizer Inc, Tempus; Nonrelevant Financial Relationships: Mashup Media LLC, MJH Life Sciences, PeerView.

MODERATOR
Sumanta Kumar Pal, MD
Professor and Vice Chair of Academic Affairs
Department of Medical Oncology
City of Hope Comprehensive Cancer Center
Duarte, California

Travel Support: CRISPR Therapeutics, EverImmune, Exelixis Inc, Ipsen Biopharmaceuticals Inc.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from Bristol Myers Squibb, Eisai Inc, and Exelixis Inc.

Release date: March 2025
Expiration date: March 2026

Dr Hutson

Albiges L et al. Cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in previously untreated advanced renal cell carcinoma (aRCC): Final results of COSMIC-313. Genitourinary Cancers Symposium 2025;Abstract 438.

Bourlon MT et al. Final prespecified overall survival (OS) analysis of CLEAR: 4-year follow-up of lenvatinib plus pembrolizumab (L+P) vs sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC). Genitourinary Cancers Symposium 2024;Abstract 362.

Choueiri TK et al. Overall survival results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab versus placebo for the treatment of clear cell renal cell carcinoma (ccRCC). ASCO 2024;Abstract LBA359.

Choueiri TK et al. Overall survival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med 2024;390(15):1359-71. Abstract

George S et al. Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T. Genitourinary Cancers Symposium 2024;Abstract LBA360.

Grünwald V et al. Analyses on impact of tumor burden at progression and changes in IMDC from baseline in patients (pts) with advanced renal cell carcinoma (aRCC) treated with lenvatinib + pembrolizumab (L+P) in the phase 3 CLEAR trial. Genitourinary Cancers Symposium 2025;Abstract 531.

Motzer RJ et al. Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate 9ER trial. Genitourinary Cancers Symposium 2025;Abstract 439.

Motzer RJ et al. Lenvatinib plus pembrolizumab versus sunitinib in first-line treatment of advanced renal cell carcinoma: Final prespecified overall survival analysis of CLEAR, a phase III study. J Clin Oncol 2024;42(11):1222-8. Abstract

Motzer RJ et al. Final prespecified overall survival (OS) analysis of CLEAR: 4-year follow-up of lenvatinib plus pembrolizumab (L+P) vs sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC). ASCO 2023;Abstract 4502.

Powles T et al. Outcomes by IMDC risk in the COSMIC-313 phase 3 trial evaluating cabozantinib (C) plus nivolumab (N) and ipilimumab (I) in first-line advanced RCC (aRCC) of IMDC intermediate or poor risk. Genitourinary Cancers Symposium 2023;Abstract 605.

Rini BI et al. Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: 5-year analysis of KEYNOTE-426. ASCO 2023;Abstract LBA4501.

Tannir NM et al. Nivolumab plus ipilimumab (NIVO+IPI) vs sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC): Long-term follow-up data from the phase 3 CheckMate 214 trial. Genitourinary Cancers Symposium 2024;Abstract 363.

 

Dr Zhang

Braun DA et al. Beyond conventional immune-checkpoint inhibition — Novel immunotherapies for renal cell carcinoma. Nat Rev Clin Oncol 2021;18(4):199-214. Abstract

Choueiri TK et al. Tivozanib–nivolumab vs tivozanib monotherapy in patients with renal cell carcinoma (RCC) following 1 or 2 prior therapies including an immune checkpoint inhibitor (ICI): Results of the phase III TiNivo-2 study. ESMO 2024;Abstract LBA73.

Pal SK et al. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): A multicentre, randomised, open-label, phase 3 trial. Lancet 2023;402(10397):185-95. Abstract

Rini BI et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): A phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol 2020;21(1):95-104. Abstract

Zhu S et al. Combination strategies to maximize the benefits of cancer immunotherapy. J Hematol Oncol 2021;14(1):156. Abstract

 

Dr McKay

Agarwal N et al. Randomized phase II dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma. Ann Oncol 2024;35(12):1148-56. Abstract

Albiges L et al. KEYMAKER-U03 Substudy 03B: Pembrolizumab (pembro) and targeted therapy combinations for advanced clear cell renal cell carcinoma (ccRCC). Genitourinary Cancers Symposium 2025;Abstract 440.

Barata P et al. Renal cell carcinoma histologic subtypes exhibit distinct transcriptional profiles. J Clin Invest 2024;134(11):e178915. Abstract

Choueiri TK et al. Belzutifan plus cabozantinib as first-line treatment for patients with advanced clear-cell renal cell carcinoma (LITESPARK-003): An open-label, single-arm, phase 2 study. Lancet Oncol 2025;26(1):64-73. Abstract

Choueiri TK et al. Casdatifan (Cas) monotherapy in patients (pts) with previously treated clear cell renal cell carcinoma (ccRCC): Safety, efficacy and subgroup analysis across multiple doses from ARC-20, a phase 1 open-label study. Genitourinary Cancers Symposium 2025;Abstract 441.

Choueiri TK et al. Updated results from the phase 2 LITESPARK-003 study of belzutifan plus cabozantinib in patients with advanced clear cell renal cell carcinoma (ccRCC). Genitourinary Cancers Symposium 2025;Abstract 549.

Choueiri TK et al. Casdatifan in patients (pts) with previously treated clear cell renal cell cancer (ccRCC) and other solid tumors; preliminary results from ARC- 20: A phase 1, open-label dose-escalation and expansion study. EOORTC-NCI-AACR Symposium 2024;Abstract 4 Oral.

Choueiri TK et al. Safety profile of belzutifan monotherapy in patients with renal cell carcinoma: A pooled analysis of 4 clinical trials. KCRS 2024;Abstract 39.

Choueiri TK et al. LITESPARK-012: Pembrolizumab plus lenvatinib with or without belzutifan or quavonlimab for advanced renal cell carcinoma. Future Oncol 2023;19(40):2631-40. Abstract

Choueiri TK et al. Phase 3 LITESPARK-022: Pembrolizumab (pembro) plus hypoxia-inducible factor 2α (HIF-2α) inhibitor belzutifan as adjuvant treatment for clear cell renal cell carcinoma (ccRCC). Genitourinary Cancers Symposium 2023;Abstract TPS748.

Choueiri TK et al. Phase II LITESPARK-003 study of belzutifan in combination with cabozantinib for advanced clear cell renal cell carcinoma (ccRCC). ESMO 2023;Abstract LBA87.

de Velasco G et al. Efficacy outcomes with belzutifan versus everolimus by baseline disease characteristics and burden subgroups in the phase 3 LITESPARK-005 study. Genitourinary Cancers Symposium 2025;Abstract 538.

Jonasch E et al. NKT2152, a novel oral HIF-2α inhibitor, in participants (pts) with previously treated advanced clear cell renal carcinoma (accRCC): Preliminary results of a phase I/II study. ESMO 2024;Abstract 16900.

Jonasch E et al. Belzutifan for renal cell carcinoma in von Hippel-Lindau disease. N Engl J Med 2021;385(22):2036-46. Abstract

Motzer RJ et al. LITESPARK-011: Belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy. Future Oncol 2023;19(2):113-21. Abstract

Pezzicoli G et al. Genomic profiling and molecular characterization of clear cell renal cell carcinoma. Curr Oncol 2023;30(10):9276-90. Abstract

Rini BI et al. Final analysis of the phase III LITESPARK-005 study of belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC). ESMO 2024;Abstract LBA74.

 

Dr Pal

Albiges L et al. Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): A single-arm, multicentre, phase 2 trial. Lancet Oncol 2023;24(8):881-91. Abstract

Alhalabi O et al. Immune checkpoint therapy combinations in adult advanced MiT family translocation renal cell carcinomas. Oncologist 2023;28(5):433-9. Abstract

Bakouny Z et al. Integrative clinical and molecular characterization of translocation renal cell carcinoma. Cell Rep 2022;38(1):110190. Abstract

Barata P et al. Final overall survival analysis of S1500: A randomized, phase II study comparing sunitinib with cabozantinib, crizotinib, and savolitinib in advanced papillary renal cell carcinoma. J Clin Oncol 2024;42(33):3911-6. Abstract

Fitzgerald KN et al. Cabozantinib plus nivolumab in patients with non-clear cell renal cell carcinoma: Updated results from a phase 2 trial. Eur Urol 2024;86(2):90-4. Abstract

Hutson TE et al. A single-arm, multicenter, phase 2 study of lenvatinib plus everolimus in patients with advanced non-clear cell renal cell carcinoma. Eur Urol 2021;80(2):162-70. Abstract

McGregor BA et al. Results of a multicenter phase II study of atezolizumab and bevacizumab for patients with metastatic renal cell carcinoma with variant histology and/or sarcomatoid features. J Clin Oncol 2020;38(1):63-70. Abstract

Montenegro GLB et al. A phase 2 study of bevacizumab, erlotinib, and atezolizumab in subjects with advanced hereditary leiomyomatosis and renal cell cancer (HLRCC) associated or sporadic papillary renal cell cancer (pRCC). ASCO 2022;Abstract 5004.

Naik P et al. The incidence, pathogenesis, and management of non-clear cell renal cell carcinoma. Ther Adv Urol 2024:16. Abstract

Pal SK et al. A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: A randomised, open-label, phase 2 trial. Lancet 2021;397(10275):695-703. Abstract

Pal SK et al. Cabozantinib in combination with atezolizumab for advanced renal cell carcinoma: Results from the COSMIC-021 study. J Clin Oncol 2021;39(33):3725-36. Abstract

Procopio G et al. Cabozantinib as first-line treatment in patients with metastatic collecting duct renal cell carcinoma: Results of the BONSAI trial for the Italian Network for Research in Urologic-Oncology (Meet-URO 2 Study). JAMA Oncol 2022;8(6):910-3. Abstract

Salgia NJ et al. Renal cell carcinoma of variant histology: New biologic understanding leads to therapeutic advances. Am Soc Clin Oncol Educ Book 2024;44(3):e438642. Abstract

Sharma MR et al. A phase I first-in-human study of XL092 in patients (pts) with locally advanced or metastatic solid tumors: Results from dose-escalation of XL092 alone and in combination with atezolizumab. ESMO 2022;Abstract 481P.

Suarez C et al. Phase II study investigating the safety and efficacy of savolitinib and durvalumab in metastatic papillary renal cancer (CALYPSO). J Clin Oncol 2023;41(14):2493-502. Abstract

Voss MH et al. First-line pembrolizumab plus lenvatinib for non–clear cell renal carcinomas (nccRCC): Extended follow-up of the phase 2 KEYNOTE-B61 study. Genitourinary Cancers Symposium 2024;Abstract 2.

Wiele AJ et al. Efficacy and safety of bevacizumab plus erlotinib in patients with renal medullary carcinoma. Cancers (Basel) 2021;13(9):2170. Abstract

Wilson NR et al. Efficacy and safety of gemcitabine plus doxorubicin in patients with renal medullary carcinoma. Clin Genitourin Cancer 2021;19(6):e401-8. Abstract