Article Text

Download PDFPDF

347 KEYNOTE-365 cohort C: pembrolizumab + enzalutamide in patients with abiraterone acetate–pretreated metastatic castration-resistant prostate cancer (mCRPC)—data after minimum of 22 months of follow-up
  1. Leonard Appleman1,
  2. Tilman Todenhoefer2,
  3. William Berry3,
  4. Howard Gurney4,
  5. Margitta Retz5,
  6. Henry Conter6,
  7. Brigitte Laguerre7,
  8. Peter Fong8,
  9. Cristiano Ferrario9,
  10. Gwenaelle Gravis10,
  11. Josep Piulats11,
  12. Urban Emmenegger12,
  13. Neal Shore13,
  14. Emanuela Romano14,
  15. Loic Mourey15,
  16. Xin Tong Li16,
  17. Christian Poehlein16,
  18. Charles Schloss16,
  19. Johann De Bono17 and
  20. Evan Yu18
  1. 1UPMC, Pittsburgh, PA, USA
  2. 2Studienpraxis Urologie, Nürtingen, Germany
  3. 3Duke Cancer Center Cary, Cary, NC, USA
  4. 4Westmead Hospital and Macquarie University Hospital, Sydney, Australia
  5. 5Klinikum rechts der Isar, Technische Universität München, Munich, Germany
  6. 6University of Western Ontario, brampton, Canada
  7. 7Center Eugéne Marquis, Rennes, France
  8. 8Auckland City Hospital, Auckland, New Zealand
  9. 9Jewish General Hospital, Montreal, Canada
  10. 10Institut Paoli Calmettes, Marseille, France
  11. 11Catalan Institute of Oncology, Barcelona, Spain
  12. 12Odette Cancer Centre, Toronto, Canada
  13. 13Carolina Urologic Research Center, Myrtle Beach, SC, USA
  14. 14Center for Cancer Immunotherapy, Institut Curie, Paris, France
  15. 15Insitut Universitaire du Cancer–Oncopole, Toulouse, France
  16. 16Merck and Co., Inc., Kenilworth, NJ, USA
  17. 17The Royal Marsden NHS Foundation Trust, London, UK
  18. 18University of Washington, Seattle, WA, USA


Background Previous data from cohort C of phase 1b/2 study KEYNOTE-365 (NCT02861573) showed that PD-1 inhibitor pembrolizumab + enzalutamide was well tolerated and showed antitumor activity in patients with abiraterone acetate–pretreated mCRPC. Updated data after a minimum of 22 months of follow-up are presented.

Methods Patients in the prechemotherapy mCRPC state who were intolerant to ≥4 weeks‘ treatment with abiraterone acetate or for whom this treatment failed, had progressive disease ≤6 months before screening, and had ECOG PS 0-2 were enrolled. Patients received pembrolizumab 200 mg IV Q3W + enzalutamide 160 mg orally QD. Primary end points were PSA response rate (decrease ≥50% from baseline), confirmed ORR per RECIST v1.1 by blinded independent central review (BICR), and safety. Secondary end points were time to PSA progression; DCR (CR or PR of any duration + SD or non-CR/non-PD ≥6 months) and DOR per RECIST v1.1 by BICR; rPFS per PCWG3-modified RECIST v1.1 by BICR; and OS.

Results Of 103 enrolled patients, 102 were treated. Median age was 70.0 years (range, 43–87); 29.4% of patients were PD-L1+; 37.3% had RECIST-measurable disease. Median follow-up (time from enrollment to data cutoff) was 40.2 months (range, 22.3–49.9). Confirmed PSA response rate in patients with baseline PSA measurement (N = 101) was 23.8%. Median time to PSA progression was 4.0 months (95% CI, 3.5–4.4). In 38 patients with measurable disease, ORR was 10.5% (2 CR; 2 PR). Median DOR was 11.8 months (4.3 to 38.3+ months); 1 patient had a response ≥12 months. DCR for the total population was 33.3%. Median (95% CI) rPFS was 6.0 months (4.1–6.3); rPFS at 12 months was 30.1%. Median (95% CI) OS was 20.1 months (16.9–25.2); OS at 12 months was 76.2%. Treatment-related AEs (TRAEs) occurred in 92.2% of patients; most common (≥20%) were fatigue (39.2%), nausea (21.6%), and rash (21.6%). Grade 3–5 TRAEs occurred in 42.2%, most commonly rash (7.8%) and fatigue (5.9%). Four patients died of AEs: 1 death was treatment-related (unknown cause).

Conclusions After a minimum follow-up of 22 months, pembrolizumab + enzalutamide continued to show antitumor activity in abiraterone acetate–pretreated mCRPC. The safety profile of pembrolizumab + enzalutamide was generally consistent with individual profiles of each agent. There was a higher incidence than typically reported for the individual agents of all-grade (21.6%) and grade 3 (7.8%) rash, which resolved with standard-of-care treatment. The combination is being further evaluated in the phase 3 study KEYNOTE-641.

Acknowledgements Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

ClinicalTrials gov, identifier: NCT02861573

Ethics Approval The study and the protocol were approved by the Institutional Review Board or ethics committee at each site.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.