Sequencing Targeted Therapy in Advanced Renal Cell Carcinoma

Dr. Voss and Dr. Serzan discuss treatment options and sequencing after progression on first-line immunotherapy-based therapy in advanced renal cell carcinoma (RCC). Dr. Serzan describes TKI monotherapy as a standard approach in this setting and reviews emerging evidence supporting combination strategies, including lenvatinib plus everolimus. He discusses the phase 2 LenCab study comparing lenvatinib plus everolimus with cabozantinib, noting improvements in objective response and progression-free survival with the combination, without a demonstrated overall survival benefit, alongside greater toxicity. The experts consider how these findings may influence treatment selection for patients who require a stronger response after progression. Dr. Serzan notes that the prospective data have increased his interest in combination therapy for appropriately selected patients, while emphasizing the potential impact of increased toxicity on quality of life. Dr. Voss similarly highlights the importance of matching treatment intensity to disease behavior, suggesting that patients with more aggressive progression or a strong need for tumor shrinkage may be better candidates for combination therapy, whereas patients with more indolent disease may be adequately managed with TKI monotherapy.