There is an unmet need for therapeutic options that prolong survival for patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC). The phase III, open-label KEYLYNK-010 study evaluated pembrolizumab plus olaparib versus a next-generation hormonal agent (NHA) for biomarker-unselected, previously treated mCRPC.
Eligible participants had mCRPC that progressed on or after abiraterone or enzalutamide (but not both) and docetaxel. Participants were randomly assigned (2:1) to pembrolizumab plus olaparib or NHA (abiraterone or enzalutamide). The dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group-modified RECIST 1.1 and overall survival (OS). Time to first subsequent therapy (TFST) was a key secondary end point. Safety and objective response rate (ORR) were secondary end points.
Between May 30, 2019, and July 16, 2021, 529 participants were randomly assigned to pembrolizumab plus olaparib and 264 to NHA. At final rPFS analysis, median rPFS was 4.4 months (95% CI, 4.2 to 6.0) with pembrolizumab plus olaparib and 4.2 months (95% CI, 4.0 to 6.1) with NHA (hazard ratio [HR], 1.02; 95% CI, 0.82 to 1.25; P = .55). At final OS analysis, median OS was 15.8 months (95% CI, 14.6 to 17.0) and 14.6 months (95% CI, 12.6 to 17.3), respectively (HR, 0.94; 95% CI, 0.77 to 1.14; P = .26). At final TFST analysis, median TFST was 7.2 months (95% CI, 6.7 to 8.1) versus 5.7 months (95% CI, 5.0 to 7.1), respectively (HR, 0.86; 95% CI, 0.71 to 1.03). ORR was higher with pembrolizumab plus olaparib versus NHA (16.8% v 5.9%). Grade ≥3 treatment-related adverse events occurred in 34.6% and 9.0% of participants, respectively.
Pembrolizumab plus olaparib did not significantly improve rPFS or OS versus NHA in participants with biomarker-unselected, heavily pretreated mCRPC. The study was stopped for futility. No new safety signals occurred.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023 Jun 08 [Epub ahead of print]
Emmanuel S Antonarakis, Se Hoon Park, Jeffrey C Goh, Sang Joon Shin, Jae Lyun Lee, Niven Mehra, Ray McDermott, Núria Sala-Gonzalez, Peter C Fong, Richard Greil, Margitta Retz, Juan Pablo Sade, Patricio Yanez, Yi-Hsiu Huang, Stephen D Begbie, Rustem Airatovich Gafanov, Maria De Santis, Eli Rosenbaum, Michael P Kolinsky, Felipe Rey, Kun-Yuan Chiu, Guilhem Roubaud, Gero Kramer, Makoto Sumitomo, Francesco Massari, Hiroyoshi Suzuki, Ping Qiu, Jinchun Zhang, Jeri Kim, Christian H Poehlein, Evan Y Yu
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD., Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Royal Brisbane & Women's Hospital, Herston, Australia., Severance Hospital Yonsei University Health System, Seoul, South Korea., Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea., Radboud University Medical Center, Nijmegen, The Netherlands., St Vincent's University Hospital, Cancer Trials Ireland, Dublin, Ireland., Institut Català d Oncologia Girona, Hospital Josep Trueta, Girona, Spain., Auckland City Hospital, University of Auckland, Auckland, New Zealand., Salzburg Cancer Research Institute-CCCIT Gmbh, Paracelsus Medical University Salzburg, Cancer Cluster Salzburg, Salzburg, Austria., Rechts der Isar Medical Center, Technical University Munich, Munich, Germany., Instituto Medico Alexander Fleming, Buenos Aires, Argentina., James Lind Cancer Research Center, Universidad de La Frontera, Temuco, Chile., Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan., Port Macquarie Base Hospital, Port Macquarie, Australia., Russian Scientific Center of Roentgenoradiology, Moscow, Russian Federation., Charité Universitaetsmedizin Berlin-Campus Mitte, Berlin, Germany., Rabin Medical Center, Petach-Tikwa, Israel., Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada., Clinica CIDO, Temuco, Chile., Taichung Veterans General Hospital, Taichung, Taiwan., Institut Bergonié, Bordeaux, France., Department of Urology, Medical University of Vienna, Vienna, Austria., Fujita Health University Hospital, Toyoake, Japan., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Toho University Sakura Medical Center, Chiba, Japan., Merck & Co, Inc, Rahway, NJ., Fred Hutchinson Cancer Center, University of Washington, Seattle, WA.