Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial

Author(s): Emmanuel S. Antonarakis , MD1,2; Se Hoon Park , MD, PhD3; Jeffrey C. Goh , MBBS, FRACP4; Sang Joon Shin, MD, PhD5; Jae Lyun Lee , MD, PhD6; Niven Mehra , MD, PhD7; Ray McDermott , MD, PhD8; Núria Sala-Gonzalez, MD9; Peter C. Fong , MBBS, FRACP10; Richard Greil, MD11; Margitta Retz, MD, PhD12; Juan Pablo Sade, MD13; Patricio Yanez, MD14; Yi-Hsiu Huang , MD, PhD15; Stephen D. Begbie , MD16; Rustem Airatovich Gafanov , MD17; Maria De Santis, MD18,19; Eli Rosenbaum, MD20; Michael P. Kolinsky, MD, FRCPC21; Felipe Rey , MD22; Kun-Yuan Chiu23; Guilhem Roubaud, MD24; Gero Kramer, MD25; Makoto Sumitomo , MD, PhD26; Francesco Massari , MD27; Hiroyoshi Suzuki, MD, PhD28; Ping Qiu , PhD29; Jinchun Zhang , PhD29; Jeri Kim, MD, MBA29; Christian H. Poehlein, MD29; and Evan Y. Yu , MD30
Source: DOI: 10.1200/JCO.23.00233 Journal of Clinical Oncology 41, no. 22 (August 01, 2023) 3839-3850.
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Pembrolizumab plus olaparib did not significantly improve radiographic progression-free survival or overall survival versus new generation hormonal agent and was more toxic.

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Author Affiliations

1Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; 2Current Address: University of Minnesota Masonic Cancer Center, Minneapolis, MN; 3Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 4Royal Brisbane & Women’s Hospital, Herston, Australia; 5Severance Hospital Yonsei University Health System, Seoul, South Korea; 6Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; 7Radboud University Medical Center, Nijmegen, The Netherlands; 8St Vincent’s University Hospital, Cancer Trials Ireland, Dublin, Ireland; 9Institut Català d Oncologia Girona, Hospital Josep Trueta, Girona, Spain; 10Auckland City Hospital, University of Auckland, Auckland, New Zealand; 11Salzburg Cancer Research Institute-CCCIT Gmbh, Paracelsus Medical University Salzburg, Cancer Cluster Salzburg, Salzburg, Austria; 12Rechts der Isar Medical Center, Technical University Munich, Munich, Germany; 13Instituto Medico Alexander Fleming, Buenos Aires, Argentina; 14James Lind Cancer Research Center, Universidad de La Frontera, Temuco, Chile; 15Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan; 16Port Macquarie Base Hospital, Port Macquarie, Australia; 17Russian Scientific Center of Roentgenoradiology, Moscow, Russian Federation; 18Charité Universitaetsmedizin Berlin—Campus Mitte, Berlin, Germany; 19Medical University of Vienna, Vienna, Austria; 20Rabin Medical Center, Petach-Tikwa, Israel; 21Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada; 22Clinica CIDO, Temuco, Chile; 23Taichung Veterans General Hospital, Taichung, Taiwan; 24Institut Bergonié, Bordeaux, France; 25Department of Urology, Medical University of Vienna, Vienna, Austria; 26Fujita Health University Hospital, Toyoake, Japan; 27Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 28Toho University Sakura Medical Center, Chiba, Japan; 29Merck & Co, Inc, Rahway, NJ; 30Fred Hutchinson Cancer Center, University of Washington, Seattle, WA

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