This segment transitions to the rationale for studying new treatment strategies in the post–PD-(L)1 setting, focusing on the lack of a clear standard of care after progression on immunotherapy. The discussion highlights that existing targeted therapies were largely developed before immune checkpoint inhibitors became widely used, leaving a gap in evidence for patients treated with modern regimens. Dr. Voss outlines the hypothesis that combining a HIF-2α inhibitor with a VEGF TKI may improve outcomes compared with TKI monotherapy. This approach aims to target complementary pathways involved in tumor growth and angiogenesis. The segment introduces the LITESPARK-011 study as a phase 3 trial designed to test this concept by comparing belzutifan plus lenvatinib with cabozantinib in patients with advanced RCC following prior PD-(L)1 therapy. The discussion sets up the biological and clinical rationale for the combination strategy evaluated in the study.
