Article Text

Download PDFPDF

351 KEYNOTE-365 cohort D: pembrolizumab plus abiraterone acetate and prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC)
  1. Josep Piulats1,
  2. Cristiano Ferrario2,
  3. Mark Linch3,
  4. Michael Stoeckle4,
  5. Brigitte Laguerre5,
  6. Jose Arranz6,
  7. Tilman Todenhoefer7,
  8. Peter Fong8,
  9. William Berry9,
  10. Urban Emmenegger10,
  11. Loic Mourey11,
  12. Nataliya Mar12,
  13. Leonard Appleman13,
  14. Anthony Joshua14,
  15. Henry Conter15,
  16. Xin Tong Li16,
  17. Charles Schloss16,
  18. Christian Poehlein16,
  19. Johann De Bono17 and
  20. Evan Yu18
  1. 1Catalan Institute of Oncology, Barcelona, Spain
  2. 2Jewish General Hospital, Montreal, Canada
  3. 3University College London Hospital, London, UK
  4. 4Saarland University Hospital, Hamburg, Germany
  5. 5Center Eugéne Marquis, Rennes, France
  6. 6Hospital Universitario Gregorio Maranon, Madrid, Spain
  7. 7Studienpraxis Urologie, Nürtingen, Germany
  8. 8Auckland City Hospital, Auckland, New Zealand
  9. 9Duke Cancer Center Cary, Cary, NC, USA
  10. 10Odette Cancer Centre, Toronto, Canada
  11. 11Insitut Universitaire du Cancer–Oncopole, Toulouse, France
  12. 12UCI Medical Center, Orange, CA, USA
  13. 13UPMC, Pittsburgh, PA, USA
  14. 14Saint Vincent’s Hospital Sydney, Sydney, Australia
  15. 15University of Western Ontario, Brampton, Canada
  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 Treatment with abiraterone acetate + prednisone can improve outcomes in mCRPC patients with or without prior chemotherapy. Cohort D of phase 1b/2 study KEYNOTE-365 (NCT02861573) evaluated safety and efficacy of PD-1 inhibitor pembrolizumab + abiraterone acetate and prednisone in patients who had not received chemotherapy for mCRPC.

Methods Patients were enrolled who had not received second-generation hormonal manipulation for mCRPC or failed/were intolerant to enzalutamide for mCRPC; had progressive disease ≤6 months before screening; and had ECOG PS 0/1. Patients received pembrolizumab 200 mg IV Q3W + abiraterone acetate 1000 mg orally QD and prednisone 5 mg orally BID. Primary end points: safety, PSA response rate (PSA decrease ≥50% from baseline), and confirmed ORR per RECIST v1.1 by blinded independent central review (BICR). Secondary end points: rPFS per PCWG3-modified RECIST v1.1, DCR, DOR, and OS.

Results One hundred three patients were treated. Median (range) age was 70.0 (46–89) years, 30.1% were PD-L1+, 35.9% had RECIST-measurable disease, 18.4% had visceral disease, and 26.2% had previously received enzalutamide only. Median (range) time from enrollment to data cutoff was 17.6 (9.7–27.0) months. Confirmed PSA response rate in patients with PSA measurement at baseline (n=103) was 56.3%. For 37 patients with RECIST-measurable disease, ORR was 16.2% (1 CR; 5 PRs); 2 patients with RECIST-nonmeasurable disease had CR. In total population, 5 patients had a response ≥6 months; DCR was 44.7%. ORR for RECIST-measurable patients was 7.7% for those who previously received enzalutamide only (n=13) and 21.7% for those who had not previously received NHAs (n=23); DCR was 11.1% in all patients who previously received enzalutamide (n=27) and 57.3% in all patients who had not received NHAs (n=75). Median (95% CI) rPFS was 15.1 (9.2-NR) months; rPFS at 12 months was 54.9%. Median (95% CI) OS was NR (23.3 months-NR); OS at 12 months was 82.9%. Sixty-nine patients (67.0%) discontinued treatment, mostly because of progressive disease (37.9%). Treatment-related AEs (TRAEs) were experienced by 90.3% of patients and most common (≥15%) were ALT increase (22.3%), AST increase (17.5%), asthenia (16.5%), and diarrhea (16.5%); 36.9% experienced grade 3–5 TRAEs. There were 18.4%/12.5% grade 3 or 4 ALT/AST laboratory elevations. Five patients died of AEs; 1 was treatment related (myasthenic syndrome).

Conclusions Pembrolizumab + abiraterone acetate and prednisone demonstrated antitumor activity in patients with chemotherapy-naive mCRPC. Safety was generally consistent with individual profiles of each agent. There was an increased incidence of grade 3–4 ALT/AST laboratory elevations.

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.