Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma

作者：Toni K. Choueiri, Piotr Tomczak, Se Hoon Park, Balaji Venugopal, Tom Ferguson, Stefan N. Symeonides, Jaroslav Hájek, Yen-Hwa Chang, Jae‐Lyun Lee, Naveed Sarwar, Naomi B. Haas, Howard Gurney, Piotr Sawrycki, Mauricio Mahave, Marine Gross‐Goupil, Tian Zhang, John M. Burke, Gurjyot K. Doshi, Bohuslav Melichar, Evgeniy Kopyltsov, Ajjai Alva, Stéphane Oudard, Delphine Topart, Hans J. Hammers, Hiroshi Kitamura, David F. McDermott, Adriano da Silva, Eric Winquist, Jerry Cornell, Aymen Elfiky, Joseph E. Burgents, Rodolfo F. Perini, Thomas Powles · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2312695 · 被引用次数：311 · 研究领域：Renal cell carcinoma treatment、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

BACKGROUND: Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain. METHODS: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent. A significant improvement in disease-free survival according to investigator assessment (the primary end point) was shown previously. Overall survival was the key secondary end point. Safety was a secondary end point. RESULTS: A total of 496 participants were assigned to receive pembrolizumab and 498 to receive placebo. As of September 15, 2023, the median follow-up was 57.2 months. The disease-free survival benefit was consistent with that in previous analyses (hazard ratio for recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87). A significant improvement in overall survival was observed with pembrolizumab as compared with placebo (hazard ratio for death, 0.62; 95% CI, 0.44 to 0.87; P = 0.005). The estimated overall...