RCT: : Belzutifan Improves Progression-Free Survival and Objective Response Compared to Everolimus in Advanced Renal-Cell Carcinoma – N Engl J Med

Study Design and Population: This phase 3, multicenter, open-label trial included 746 participants with advanced clear-cell renal-cell carcinoma who had previously undergone immune checkpoint and antiangiogenic therapies. Participants were randomly assigned to receive either belzutifan (120 mg daily) or everolimus (10 mg daily) until disease progression or intolerable toxicity occurred.

Main Findings: The median progression-free survival was identical at 5.6 months for both groups. However, at 18 months, a significantly higher percentage of participants in the belzutifan group (24.0%) remained progression-free compared to the everolimus group (8.3%, P=0.002). Belzutifan also led to a significantly higher objective response rate (21.9% vs. 3.5%, P<0.001). Median overall survival was similar between the groups, with no significant difference (21.4 months vs. 18.1 months, P=0.20).

Implications for Practice: Belzutifan offers a substantial benefit in progression-free survival and objective response rate over everolimus in patients with advanced renal-cell carcinoma post previous therapies. It was well-tolerated, with safety comparable to everolimus, suggesting its potential as a preferred treatment option in this patient population.

Reference: Choueiri TK, Powles T, Peltola K, et al. (2024). Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma. N Engl J Med, 391(8), 710-721. DOI: 10.1056/NEJMoa2313906. https://www.nejm.org/doi/full/10.1056/NEJMoa2313906