Belzutifan Plus Lenvatinib Versus Cabozantinib for Advanced Renal Cell Carcinoma After Anti–PD-(L)1 Therapy: Open-Label Phase 3 LITESPARK-011 Study

Martin Voss, MD, discusses findings from the phase 3 LITESPARK-011 trial evaluating belzutifan plus lenvatinib versus cabozantinib in patients with previously treated metastatic clear cell renal cell carcinoma. The global randomized study enrolled patients whose disease progressed after prior immune checkpoint inhibitor–based therapy and compared the investigational combination with standard cabozantinib monotherapy. Results demonstrated a statistically significant improvement in progression-free survival with belzutifan plus lenvatinib, with a median progression-free survival of 14.8 months versus 10.7 months for cabozantinib. The combination also produced a higher objective response rate and longer duration of response. Overall survival favored the investigational regimen numerically but did not reach statistical significance at the interim analysis. As expected, combination therapy was associated with higher rates of treatment-related adverse events, including anemia, fatigue, and hypoxia, although some kinase inhibitor–associated toxicities were less frequent. These findings suggest belzutifan plus lenvatinib may represent a promising treatment strategy following checkpoint inhibitor therapy in advanced renal cell carcinoma.