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 , MD^1,2; 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, MD^18,19; 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.

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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