First-Line Therapy in Clear Cell Renal Cell Carcinoma
Brian Rini, MD; Arpita Desai, MD; Sundhar Ramalingam, MD; and Scott Tykodi, MD, PhD, discuss how to select among the 4 major FDA-approved immunotherapy-based doublet regimens (ipilimumab-nivolumab, pembrolizumab-axitinib, nivolumab-cabozantinib, and pembrolizumab-lenvatinib) for first-line treatment of clear cell renal cell carcinoma, considering factors such as disease burden, patient comorbidities, toxicity profiles, and individual patient preferences while reviewing long-term efficacy data and discussing future therapeutic directions, including novel immunotherapies and biomarker development.
EP. 1: Overview of Clear Cell Renal Cell Carcinoma
August 29th 2025Panelists discuss how clear cell renal cell carcinoma (RCC) represents the most common kidney cancer subtype, typically affecting men in their 50s and 60s who often present incidentally with metastatic disease, and has limited identifiable risk factors beyond smoking, hypertension, and obesity.
EP. 2: Clinical Trial Review: CheckMate 214
August 29th 2025Panelists discuss how the CheckMate 214 study demonstrated durable overall survival benefits with ipilimumab plus nivolumab vs sunitinib, with 9-year follow-up showing improved outcomes even in favorable-risk patients and nearly half of responders remaining in remission.
EP. 3: Clinical Trial Review: KEYNOTE-426
September 8th 2025Panelists discuss how the KEYNOTE-426 trial established pembrolizumab plus axitinib as an effective and well-tolerated immunotherapy-tyrosine kinase inhibitor (IO-TKI) combination with high response rates and unprecedented tumor control, particularly suitable for frail patients due to axitinib's selective targeting and short half-life.
EP. 4: Clinical Trial Review: CheckMate 9ER
September 8th 2025Panelists discuss how CheckMate 9ER results demonstrated significant progression-free survival and overall survival benefits with nivolumab plus cabozantinib vs sunitinib, with particularly impressive HRs for patients with visceral disease, including liver, bone, and lung metastases.
EP. 5: Clinical Trial Review: CLEAR
September 15th 2025Panelists discuss how the CLEAR trial showed pembrolizumab plus lenvatinib achieved the highest objective response rate (71%) and progression-free survival (23.3 months) among frontline regimens, though requiring careful patient selection due to lenvatinib's challenging toxicity profile at the full 20 mg dose.
EP. 6: First-Line Treatment Selection
September 15th 2025Panelists discuss how treatment selection for a typical intermediate-risk patient with clear cell renal cell carcinoma (RCC) involves choosing between ipilimumab plus nivolumab for long-term durable responses in nonsymptomatic patients and immunotherapy-tyrosine kinase inhibitor (IO-TKI) combinations for those requiring rapid disease control or cytoreduction.
EP. 7: Treatment Selection in Favorable Risk and Progression Considerations
September 22nd 2025Panelists discuss how favorable-risk patients may be candidates for active surveillance if their disease is indolent, while treatment decisions should consider the long-term survival benefits of ipilimumab plus nivolumab vs the higher response rates of immunotherapy-tyrosine kinase inhibitor (IO-TKI) combinations, with pseudoprogression being relatively rare in clinical practice.
EP. 8: Adverse Event Management Strategies
September 22nd 2025Panelists discuss how toxicity considerations significantly influence treatment selection given multiple effective options, requiring personalized discussions about patient goals, comorbidities, and tolerance for different adverse effect profiles between immune therapy doublets and immunotherapy-tyrosine kinase inhibitor (IO-TKI) combinations.
