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.