First-Line Therapy in Clear Cell Renal Cell Carcinoma

Panelists 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.

Panelists 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.

Panelists 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.

Panelists 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.

Panelists 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.

Panelists 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.

Panelists 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.

Panelists 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.

Panelists discuss how the future of renal cell carcinoma (RCC) treatment lies in developing better biomarkers for patient selection, novel immune therapies including chimeric antigen receptor (CAR) T cells and T-cell engagers, HIF-alpha inhibitors, radioligand therapies, and moving beyond the current immunotherapy-based doublet paradigm that has dominated for 7 years.