Pembrolizumab plus enzalutamide versus placebo plus enzalutamide for chemotherapy-naive metastatic castration-resistant prostate cancer: the randomized, double-blind, phase III KEYNOTE-641 study

作者：Jeremy Graff, Mauricio Burotto, P.C. Fong, David Pook, B. Zurawski, Ray Manneh Kopp, Jorge Salinas, Kathryn Bylow, Gero Kramer, Raffaele Ratta, Mariusz Kwiatkowski, M. Retz, Cheol Kwak, Jóse Ángel Arranz Arija, Howard Gurney, N. Matsubara, Lorea Villanueva, T. Todenhöfer, Li Liang, Jelena Todoric, K. Imai, Arnulf Stenzl · 发表于：Annals of Oncology · 年份：2025 · DOI：10.1016/j.annonc.2025.05.007 · 被引用次数：17 · 研究领域：Prostate Cancer Treatment and Research、Prostate Cancer Diagnosis and Treatment、Radiopharmaceutical Chemistry and Applications

BACKGROUND: Established first- and second-line standard-of-care treatment options (abiraterone, enzalutamide, taxane chemotherapy) are available for patients with metastatic castration-resistant prostate cancer (mCRPC), but almost all patients experience subsequent disease progression. The randomized, double-blind, phase III KEYNOTE-641 study evaluated pembrolizumab plus enzalutamide versus placebo plus enzalutamide in participants with chemotherapy-naive mCRPC. PATIENTS AND METHODS: Eligible participants were males aged ≥18 years with confirmed mCRPC and no prior chemotherapy except docetaxel in the hormone-sensitive setting. Prior abiraterone treatment was permitted. Participants were randomly assigned 1:1 to receive pembrolizumab 200 mg or placebo intravenously once every 3 weeks for ≤35 cycles plus enzalutamide 160 mg orally daily. Dual primary end points were overall survival (OS) and radiographic progression-free survival (rPFS) per Prostate Cancer Clinical Trials Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review. Safety was a secondary end point. RESULTS: Between 21 August 2019, and 10 June 2022, 1244 participants were randomly assigned to pembrolizumab plus enzalutamide (n = 621) or placebo plus enzalutamide (n = 623). At the data cut-off date (12 December 2022), median follow-up was 27.6 months (range, 6.1-39.8 months). Primary end points of OS [median, 24.7 versus 27.3 months; h...