The standard of care for metastatic castration-resistant prostate cancer (mCRPC) after second-generation androgen receptor pathway inhibitor (ARPI) therapy is still docetaxel. The randomized, double-blind, phase III KEYNOTE-921 trial (Clinicaltrials. gov identifier: NCT03834506) evaluated the efficacy and safety of pembrolizumab or placebo plus docetaxel for previously treated mCRPC.
Adults with mCRPC who progressed after androgen-deprivation therapy and one ARPI were randomly assigned 1:1 to pembrolizumab or placebo plus docetaxel with concomitant prednisone. Dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group 3-modified RECIST 1.1 and overall survival (OS). Safety was a secondary end point.
Between May 30, 2019, and June 17, 2021, 515 participants were randomly assigned to pembrolizumab plus docetaxel and 515 to placebo plus docetaxel. Median time from random assignment to data cutoff date (June 20, 2022) at final analysis (FA) was 22.7 months (range, 12.1-36.7). At first interim analysis (data cutoff date: September 27, 2021), median rPFS was 8.6 months (95% CI, 8.3 to 10.2) with pembrolizumab plus docetaxel versus 8.3 months (95% CI, 8.2 to 8.5) with placebo plus docetaxel (hazard ratio [HR], 0.85 [95% CI, 0.71 to 1.01]; P = .03). At FA, median OS was 19.6 months (95% CI, 18.2 to 20.9) versus 19.0 months (95% CI, 17.9 to 20.9), respectively (HR, 0.92 [95% CI, 0.78 to 1.09]; P = .17). Grade ≥3 treatment-related adverse events occurred in 43.2% of participants who received pembrolizumab plus docetaxel and 36.6% of participants who received placebo plus docetaxel. Two and seven participants, respectively, died due to a treatment-related adverse event. Pneumonitis was the most common immune-mediated adverse event (7.0% v 3.1%).
The addition of pembrolizumab to docetaxel did not significantly improve efficacy outcomes for participants with previously treated mCRPC. The current standard of care remains unchanged.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2025 Mar 05 [Epub ahead of print]
Daniel P Petrylak, Raffaele Ratta, Nobuaki Matsubara, Ernesto Korbenfeld, Rustem Gafanov, Loic Mourey, Tilman Todenhöfer, Howard Gurney, Gero Kramer, Andries M Bergman, Pawel Zalewski, Maria De Santis, Andrew J Armstrong, Winald Gerritsen, Russell Pachynski, Seok Soo Byun, Margitta Retz, Eric Levesque, Ray McDermott, Sergio Bracarda, Ray Manneh, Meital Levartovsky, Xin Tong Li, Charles Schloss, Christian H Poehlein, Karim Fizazi
Yale Cancer Center, New Haven, CT., Hopital Foch, Suresnes, France., National Cancer Center Hospital East, Chiba, Japan., Hospital Britanico de Buenos Aires, Buenos Aires, Argentina., Russian Scientific Center of Roentgenoradiology, Moscow, Russia., Institut Claudius Regaud IUCT Oncopole, Toulouse, France., Studienpraxis Urologie, Nürtingen, Germany., Macquarie University, Sydney, Australia., Department of Urology, Medical University of Vienna, Vienna, Austria., Netherlands Cancer Institute, Amsterdam, the Netherlands., Lakeridge Health, Oshawa, ON, Canada., Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC., Radboud University Medical Center, Nijmegen, the Netherlands., Washington University School of Medicine, St Louis, MO., Seoul National University Bundang Hospital, Seongnam, South Korea., Rechts der Isar Medical Center, Technical University Munich, Munich, Germany., CHU de Québec-Université Laval-Hôtel-Dieu de Québec, Québec City, QC, Canada., St Vincent's University Hospital, Cancer Trials Ireland, Dublin, Ireland., Azienda Ospedaliera Santa Maria Terni, Terni, Italy., Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia., Chaim Sheba Medical Center, Ramat Gan, Israel., Merck & Co, Inc, Rahway, NJ., Institut Gustave Roussy, University of Paris Saclay, Villejuif, France.