Second-Line Options and Selecting Ipilimumab Plus Nivolumab in RCC

After progression on frontline immunotherapy-based combinations, patients with advanced RCC have a growing set of options. The panel reviews cabozantinib as a consistent benchmark in the immunotherapy-experienced setting, with reproducible outcomes as the comparator arm across several randomized studies. Faculty then discuss the LITESPARK trial, in which belzutifan, a hypoxia-inducible factor inhibitor, combined with lenvatinib improved progression-free survival and produced high, durable responses compared with cabozantinib. The combination also carried somewhat greater aggregate toxicity. The conversation turns to real-world lenvatinib dosing, including lower starting doses for heavily pretreated patients and concern that routinely attenuated dosing may erode the efficacy seen in trials. The panel then revisits the frontline choice between ipilimumab plus nivolumab and an immunotherapy-TKI regimen. Dual immunotherapy has lower upfront response rates and more immune-related toxicity but offers a chance of durable, treatment-free response, which makes it well suited to asymptomatic patients. Symptomatic patients who cannot risk early progression are better served by an immunotherapy-TKI combination.