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Genitourinary tumours, prostate

3357 - Pembrolizumab for patients with advanced prostate adenocarcinoma: Preliminary results from the KEYNOTE-028 study


09 Oct 2016


Genitourinary tumours, prostate


Aaron Hansen


Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372


A. Hansen1, C. Massard2, P.A. Ott3, N. Haas4, J. Lopez5, S. Ejadi6, J. Wallmark7, B. Keam8, J. Delord9, R. Aggarwal10, M. Gould11, P. Qiu12, S. Saraf13, S. Keefe14, S.A. Piha-Paul15

Author affiliations

  • 1 Oncology, Princess Margaret Cancer Centre, M5G 2M9 - Toronto/CA
  • 2 Medicine, Istitute Gustave Roussy, Villejuif/FR
  • 3 Immunooncology, Harvard Medical School, Boston/US
  • 4 Medical Oncology, Hospital of the University of Pennsylvania, Philadelphia/US
  • 5 Medical Oncology, Institute of Cancer Research ICR, London/GB
  • 6 Clinical Trials, Virginia G. Piper Cancer Center, Scottsdale/US
  • 7 Oncology, Associates in Oncology & Hematology, Rockville/US
  • 8 Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR
  • 9 Oncology, Institut Claudius Régaud, Toulouse/FR
  • 10 Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco/US
  • 11 Clinical Research, Merck & Co, Inc., Kenilworth/US
  • 12 Genomic Biomarkers, Merck & Co, Inc., Kenilworth/US
  • 13 Biostats, Merck & Co., Inc., 07033 - Kenilworth/US
  • 14 Oncology, Merck & Co., Inc., Kenilworth/US
  • 15 Department Of Investigational Cancer Therapeutics, UT MD Anderson Cancer Center, 77030 - Houston/US


Abstract 3357


Therapies currently available for castrate-refractory prostate cancer (CRPC) provide only modest clinical benefit. Expression of the programmed death 1 (PD-1) receptor and its ligand, PD-L1, has been reported in CRPC. Pembrolizumab, an anti–PD-1 antibody, blocks the interaction between PD-1 and PD-L1. KEYNOTE-028 (NCT02054806) is a nonrandomized, phase 1b trial to evaluate the safety and efficacy of pembrolizumab in 20 advanced solid tumor cohorts. Herein are the results from the prostate adenocarcinoma cohort of this study.


Key eligibility criteria included advanced adenocarcinoma of the prostate, failure of standard therapy, measurable disease per RECIST v1.1, ECOG PS 0-1, and PD-L1 expression in ≥1% of tumor or stroma cells by immunohistochemistry. Pembrolizumab 10 mg/kg was administered every 2 weeks (wk) for up to 24 months (mo) or until disease progression (PD), intolerable toxicity, death, or withdrawal of consent. Stable patients (pts) with PD could remain on treatment until PD was confirmed by a follow-up scan. Response was assessed every 8 wk for the first 6 mo and every 12 wk thereafter. The primary end point was ORR per RECIST v1.1 by investigator review. As an exploratory objective, a NanoString platform was used to assess baseline tumor tissue for the gene expression profile (GEP) of an 18-gene panel hypothesized to be associated with a Th1-derived IFN-ɣ immune response.


Of the 23 pts enrolled in this cohort, median age was 65 years, 74% had an ECOG PS of 1 (1 pt had an ECOG PS of 2), and 74% received ≥2 prior therapies for metastatic disease. As of February 17, 2016, median follow-up duration was 33 wk (range, 6-79 wk). Fourteen pts (61%) had treatment-related adverse events (TRAEs), most commonly nausea (n = 3, 13%). Three pts (13%) had grade 3-4 TRAEs; 1 pt had grade 3 fatigue, 1 pt had grade 3 peripheral neuropathy, and 1 pt had grade 3 asthenia and grade 4 lipase increase. No pts died or discontinued pembrolizumab because of a TRAE. Three pts had a confirmed PR, for an ORR of 13% (95% CI, 3%-34%); median duration of response was 59 wk (range, 28-62 wk). Stable disease rate was 39% (n = 9; 95% CI, 20%-61%). Median OS was 8 mo, and the 6-mo PFS rate was 39%. Two pts remained on treatment at data cutoff. Exploratory assessment of the relationship between GEP score and clinical outcome revealed the putative T cell inflamed signature to be associated with better clinical outcome, consistent with pembrolizumab findings published previously.


Pembrolizumab produced durable responses among heavily pretreated pts with advanced PD-L1–positive prostate cancer. Treatment was associated with a favorable side-effect profile.

Clinical trial identification


Legal entity responsible for the study

Merck & Co. Inc.


Merck & Co., Inc.


C. Massard: Advisory Board Member: Astra Zeneca, Bayer, Celgene, Genentech, Ipsen, Jansen, Lilly, Novartis, Pfizer, Roche, Sanofi, Orion, MedImmune, New Oncology, DebioPharm.

M. Gould, P. Qiu, S. Saraf, S. Keefe: Employee, stock ownership Merck & Co., Inc.

S.A. Piha-Paul: Corporate-sponsored research: GlaxoSmithKline, Novartis, Puma Biotechnology, Inc., Merck, Sharp and Dohme, BioMarin Pharmaceutical, Inc., Principia Biopharma, Inc., Abbvie, XuanZhu Biopharma, Helix BioPharma Corp., Incyte, Inc., Curis.

All other authors have declared no conflicts of interest.

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