Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma

作者：Toni K. Choueiri, Thomas Powles, Katriina Peltola, Guillermo de Velasco, Mauricio Burotto, Cristina Suárez, Pooja Ghatalia, Roberto Iacovelli, Elaine T. Lam, Elena Verzoni, Mahmut Gümüş, Walter M. Stadler, Christian Kollmannsberger, Bohuslav Melichar, Balaji Venugopal, Marine Gross‐Goupil, Alexandr Poprach, Maria De Santis, Fabio A. Schutz, Se Hoon Park, Dmitry Nosov, Camillo Porta, Jae‐Lyun Lee, Xavier García del Muro, Elisa Biscaldi, Ray Manneh Kopp, Mototsugu Oya, He Li, Aobo Wang, Rodolfo F. Perini, Donna Vickery, Laurence Albigès, Brian I. Rini · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2313906 · 被引用次数：160 · 研究领域：Renal cell carcinoma treatment、Cancer, Hypoxia, and Metabolism、Microbial metabolism and enzyme function

BACKGROUND: Belzutifan, a hypoxia-inducible factor 2α inhibitor, showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies. METHODS: In a phase 3, multicenter, open-label, active-controlled trial, we enrolled participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies and randomly assigned them, in a 1:1 ratio, to receive 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or unacceptable toxic effects occurred. The dual primary end points were progression-free survival and overall survival. The key secondary end point was the occurrence of an objective response (a confirmed complete or partial response). RESULTS: A total of 374 participants were assigned to belzutifan, and 372 to everolimus. At the first interim analysis (median follow-up, 18.4 months), the median progression-free survival was 5.6 months in both groups; at 18 months, 24.0% of the participants in the belzutifan group and 8.3% in the everolimus group were alive and free of progression (two-sided P = 0.002, which met the prespecified significance criterion). A confirmed objective response occurred in 21.9% of the participants (95% confidence interval [CI], 17.8 to 26.5) in the belzutifan group and in 3.5% (95% CI, 1.9 to 5.9) in the everolimus group (P<0.001, which met the prespecified significance criterion). At the second interim analysis (median follow-up, 25.7 months), the m...