851PD - Subgroup Analyses from KEYNOTE-045: Pembrolizumab (pembro) Versus Individual Investigator’s Choice of Chemotherapy (paclitaxel, docetaxel, or vinfl...

Date 10 September 2017
Event ESMO 2017 Congress
Session Genitourinary tumours, non-prostate
Topics Urothelial Cancers
Genitourinary Cancers
Presenter Daniel Petrylak
Citation Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371
Authors D. Petrylak1, N.J. Vogelzang2, Y. Fradet3, D. Bajorin4, R. de Wit5, D.J. Vaughn6, J. Lee7, L. Fong8, M.A. Climent9, A. Necchi10, W.R. Gerritsen11, H. Gurney12, D.I. Quinn13, S. Culine14, C.N. Sternberg15, E. Jensen16, M. Puhlmann16, R.F. Perini16, J. Bellmunt17, T.K. Choueiri18
  • 1Medical Oncology, Yale University School of Medicine Medical Oncology, 06520-8032 - New Haven/US
  • 2Medical Oncology, Comprehensive Cancer Centers of Nevada, 89169 - Las Vegas/US
  • 3Medical Oncology, CHU de Québec-Université Laval, Quebec City/CA
  • 4Medical Oncology, Memorial Sloan Kettering Cancer Center, 10022 - New York/US
  • 5Oncology, Erasmus MC Cancer Institute, Rotterdam/NL
  • 6Medical Oncology, Abramson Cancer Center of the University of Pennsylvania, Philadelphia/US
  • 7Oncology, Asan Medical Center, University of Ulsan College of Medicine, 05505 - Seoul/KR
  • 8Medical Oncology, University of California, 94143 - San Francisco/US
  • 9Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia/ES
  • 10Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 11Medical Oncology, Radboud University Medical Centre Nijmegen, 6500 HB - Nijmegen/NL
  • 12Medical Oncology, Westmead Hospital and Macquarie University, Sydney/AU
  • 13Medical Oncology, University of Southern California Norris Comprehensive Cancer Center and Hospital, 90033 - los angeles/US
  • 14Medical Oncology, Hôpital St. Louis, 75010 - Paris/FR
  • 15Department Of Oncology, San Camillo and Forlanini Hospitals, 156 - Rome/IT
  • 16Medical Oncology, Merck & Co., Inc., Kenilworth/US
  • 17Medical Oncology, Dana-Farber Cancer Institute, 2215 - Boston/US
  • 18Medical Oncology, Dana-Farber Cancer Institute, Boston/US



In the open-label, phase 3 KEYNOTE-045 study (NCT02256436), overall survival (OS) was significantly longer with pembro vs investigator’s choice of chemo (median, 10.3 vs 7.4 mo; hazard ratio [HR], 0.73; P = 0.002) in recurrent, advanced UC. In a post hoc analysis, pembro was compared with the individual agents in the chemo arm.


Pts with histologically or cytologically confirmed UC, progression after platinum, ECOG PS 0-2, measurable disease (RECIST v1.1), and ≤2 lines of systemic therapy were randomly assigned 1:1 to pembro 200 mg Q3W or investigator’s choice of paclitaxel 175 mg/m2 Q3W, docetaxel 75 mg/m2 Q3W, or vinflunine 320 mg/m2 Q3W. Primary end points: OS and PFS (RECIST v1.1, blinded central review). ORR (RECIST v1.1, blinded central review) was a secondary end point.


525 pts were included in these analyses (allocation: pembro, 270; paclitaxel, 84; docetaxel, 84; vinflunine, 87). Baseline demographics were generally balanced among the 4 groups. Median follow-up was 14 mo (range, 10-22 mo). Pembro was associated with an OS benefit over the individual chemo agents (HR [95% CI]: paclitaxel, 0.77 [0.57-1.06]; docetaxel, 0.78 [0.56-1.08]; vinflunine, 0.71 [0.52-0.96]). PFS was similar between pembro and each of the chemo agents. ORR (95% CI) was 21% (16%-27%) with pembro vs 12% (6%-21%), 6% (2%-13%), and 18% (11%-28%) with paclitaxel, docetaxel, and vinflunine, respectively. Treatment-related AEs occurred in 61% (pembro), 88% (paclitaxel), 92% (docetaxel), and 91% (vinflunine) of pts. 15% (pembro), 44% (paclitaxel), 54% (docetaxel), and 51% (vinflunine) experienced treatment-related AEs of grade ≥3 severity.


Results from subgroup analyses of KEYNOTE-045 demonstrate that pembro was associated with longer OS, higher antitumor activity, and lower incidence of toxicities than single-agent paclitaxel, docetaxel, or vinflunine in pts with advanced UC that progressed on/after platinum-based therapy. Pembro is the first agent to demonstrate OS improvement vs chemo in this setting and should be considered for use in recurrent, advanced UC.

Clinical trial identification

NCT02256436; September 29, 2014

Legal entity responsible for the study

Merck & Co., Inc.


Merck & Co., Inc.


D. Petrylak: Ad board member: Bayer, Bellicum, Dendreon, Sanofi, J&J, Exelixis, Ferring, Millineum, Medivation, Pfizer, Roche, Tyme; Funding: Oncogenix, Progenics, J&J, Merck, Millineum, Dendreon, Sanofi, Agensys, Lilly, Roche; Stocks: Bellicum, Tyme. N.J. Vogelzang: Speaker: Medivation, Dendreon, Bayer, Caris MPI, Millennium, Sanofi, GSK, Pfizer, Genentech, Bristol-Myers Squib; Funding: PAREXEL; Progenics, Exelixis; US Oncology; Viamet; Endocyte; GSK; Merck Y. Fradet: Ad board member: Merck, Astellas, Roche, AstraZeneca; Funding: Astellas; Travel expenses: Roche. D. Bajorin: Honoraria: Merck, Genentech; Ad board: Roche, Merck, Genentech, Pfizer, AstraZeneca; Funding: Merck, Genentech, Bristol-Myers Squib, Roche, Novartis; R. de Wit: Ad board member: Merck, Roche, Sanofi, Lilly. D.J. Vaughn: Consultant: Astellas Pharma. J-L. Lee: Ad board: Astellas, AstraZeneca; Eisai; Honoraria: Pfizer, Astellas Pharma, Novartis; Funding: Pfizer, Janssen, Novartis, Exelixis. L. Fong: Funding: Dendreon, Bristol-Myers Squib, Oncosec, Abbvie, Genentech, Janssen. M.A. Climent: Honoraria: Roche, Bristol-Myers Squib, Bayer, Astellas, Sanofi, Janssen, Pfizer, Novartis; Ad board: Janseen, Pfizer, Roche, Sanofi, Astellas, Bayer; Travel expenses: Astellas, Janssen, Pfizer. W.R. Gerritsen: Ad board member: Bristol-Myers Squib, Amgen, MSD, Aglaia Biomedical Ventures, Astellas, Bayer, Janssen; Speaker: MSD, Bristol-Myers Squib; Funding: Astellas, Bayer, Janssen; Travel expenses: Amgen, Bayer. H. Gurney: Ad board: Bristol-Myers Squib, GSK, Pfizer, Astellas; Travel expenses: Astellas. D.I. Quinn: Ad board: Pfizer, Bristol-Myers Squib, Merck, EMD Serono, AstraZeneca, Genentech, Exelixis; Funding: Pfizer, Merck; Honoraria: Pfizer, Bristol-Myers Squib, Merck, EMD Serono, AstraZeneca, Genentech, Exelixis. S. Culine: Ad board: Roche, Janssen; Funding: Astellas, Roche, MSD; Travel expenses: Amgen, Astellas, Janssen. C.N. Sternberg: Honoraria: Pfizer, Bristol-Myers Squib, Novartis, Janssen, Bayer, Astellas Pharma, Sanofi, Eisai, Ipsen, GSK, MSD. E. Jensen: Employee of Merck & Co., Inc. M. Puhlmann, R. Perini: Employee of Merck & Co., Inc. J. Bellmunt: Personal fees: Merck, Genentech, Pfizer, AstraZeneca. T.K. Choueiri: Ad board: AstraZeneca, Bayer, Bristol-Myers Squib, Cerulean, Eisai, Foundation Medicine, Genetech, GSK, Merck, Novartis, Peloton, Pfizer, Prometheus, Roche, Eisai; Funding: AstraZeneca, Bristol-Myers Squib, Exelixis, Genentech, GSK, Merck, Novartis, Peloton, Pfizer, Roche, Tracon, Eisai. All other authors have declared no conflicts of interest.