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Genitourinary tumours, non-prostate

5358 - Pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine for recurrent, advanced urothelial cancer (UC): mature results from the phase 3 KEYNOTE-045 trial


10 Sep 2017


Genitourinary tumours, non-prostate


Ronald de Wit


Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440


R. de Wit1, D.J. Vaughn2, Y. Fradet3, J. Lee4, L. Fong5, N.J. Vogelzang6, M.A. Climent7, D.P. Petrylak8, T.K. Choueiri9, A. Necchi10, W.R. Gerritsen11, H. Gurney12, D.I. Quinn13, S. Culine14, C.N. Sternberg15, Y. Mai16, M. Puhlmann16, R.F. Perini16, J. Bellmunt9, D.F. Bajorin17

Author affiliations

  • 1 Medical Oncology, Erasmus MC Cancer Institute, 3075 EA - Rotterdam/NL
  • 2 Medical Oncology, Abramson Cancer Center of the University of Pennsylvania, Philadelphia/US
  • 3 Medical Oncology, CHU de Québec-Université Laval, Québec City/CA
  • 4 Medical Oncology, Asan Medical Center and University of Ulsan College of Medicine, Seoul/KR
  • 5 Medical Oncology, University of California, San Francisco, San Francisco/US
  • 6 Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas/US
  • 7 Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia/ES
  • 8 Medical Oncology, Smilow Cancer Hospital at Yale University, New Haven/US
  • 9 Medical Oncology, Dana-Farber Cancer Institute, Boston/US
  • 10 Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan/IT
  • 11 Medical Oncology, Radboud University Medical Center, Nijmegen/NL
  • 12 Medical Oncology, Westmead Hospital and Macquarie University, Sydney/AU
  • 13 Medical Oncology, University of Southern California Norris Comprehensive Cancer Center and Hospital, Los Angeles/US
  • 14 Medical Oncology, Hôpital Saint-Louis, Paris/FR
  • 15 Medical Oncology, San Camillo Forlanini Hospital, Rome/IT
  • 16 Medical Oncology, Merck & Co., Inc., Kenilworth/US
  • 17 Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York/US


Abstract 5358


In the phase 3 KEYNOTE-045 trial (NCT02256436), pembro was associated with significantly longer OS vs investigator’s choice of chemotherapy (chemo; paclitaxel, docetaxel, or vinflunine) in recurrent, advanced UC. Mature results from this open-label trial are presented.


Patients (pts) with histologically or cytologically confirmed UC, progression after platinum, ≤2 lines of systemic therapy, measurable disease (RECIST v1.1), and ECOG PS 0-2 were randomly assigned 1:1 to pembro 200 mg Q3W or paclitaxel 175 mg/m2 Q3W, docetaxel 75 mg/m2 Q3W, or vinflunine 320 mg/m2 Q3W. Primary end points: OS and PFS. Secondary end points included ORR and safety. Efficacy was assessed in all pts and pts with a PD-L1 combined positive score (CPS; % of PD-L1–expressing tumor and inflammatory cells) ≥10%.


270 pts assigned to pembro; 272 pts assigned to chemo. Baseline characteristics were generally similar between arms. As of May 19, 2017, median follow-up was 22.5 mo for both treatment arms. Median OS was significantly longer with pembro vs chemo in all pts (10.3 vs 7.4 mo; HR, 0.70; P = 0.0003) and in pts with CPS ≥10% (8.0 vs 5.2 mo; HR, 0.58; P = 0.003). OS was longer with pembro vs chemo regardless of age, liver metastases, hemoglobin, visceral disease, and choice of chemo. The 18-mo OS rate was 33.2% (95% CI, 27.5-38.9) with pembro vs 19.7% (95% CI, 14.7-24.8) with chemo (KM estimate). Median PFS was not significantly different (2.1 vs 3.3 mo; HR, 0.96; P = 0.32). ORR was 21.1% (95% CI, 16.4-26.5) (pembro) and 11.0% (95% CI, 7.6-15.4) (chemo). Responses were more durable with pembro (median [range] response duration, not reached [1.6+ to 24.6+ mo] vs 4.4 mo [1.4+ to 24.0+]). Treatment-related AEs of any grade occurred in 62.0% (pembro) and 90.6% (chemo) of pts; grade ≥3 treatment-related AEs occurred in 16.5% and 50.2%.


With additional follow-up, OS with pembro vs chemo (paclitaxel, docetaxel, or vinflunine) continues to improve (HR, 0.70 vs 0.73 at Sept 7, 2016 data cutoff) and responses continue to be more durable with pembro. Pembro also continues to have a superior safety profile compared with chemo in pts with recurrent, advanced UC.

Clinical trial identification

NCT02256436, September 29, 2014

Legal entity responsible for the study

Merck & Co., Inc.


Merck & Co., Inc.


R. de Wit: Advisory board: Merck, Roche, Sanofi, Lilly D.J. Vaughn: Grants from Merck and personal fees from Astellas. Y. Fradet: Research funding from Astellas and travel reimbursement from Roche and consultant/advisor for Merck, Astellas, Roche, and AZ. J-L. Lee: Personal fees from AstraZeneca, Astellas, Eisai and Pfizer. L. Fong: Grants from Merck, Dendreon, Bristol Myers Squibb, Roche-Genentech, Abbvie, and Amgen. N.J. Vogelzang: Consulting fee from Merck. M.A. Climent: Honoraria from Roche, BMS, Bayer, Astellas, Sanofi, Janssen, Pfizer, Novartis, consultant/advisor for Janssen, Pfizer, Roche, Sanofi, Astellas, Bayer, and travel reimbursement from Astellas, Janssen, Pfizer. D.P. Petrylak: Advisor for Bayer, Bellicum, Dendreon, Sanofi Aventis, Johnson and Johnson, Exelixis, Ferring, Millineum, Medivation, Pfizer, Roche Laboratories, (Tyme pharmaceuticals) and research funding from Oncogenix, Progenics, Johnson and Johnson, Merck, Millineum, Dendreon, Sanofi Aventis, Agensys, Eli Lilly, Roche Laboratories, and own stock in Bellicum and Tyme. T.K. Choueiri: Grants and personal fees from Merck and Pfizer. A. Necchi: Grants and personal fees from Merck, Roche, Astra Zeneca, Bayer, Millennium Takeda, Amgen and Novartis. W.R. Gerritsen: Research funding from Astellas, Bayer, and Janssen-Cilag and travel reimbursement from Amgen and Bayer, consultant/advisor for BMS, Amgen, MSD, Aglaia Biomedical Ventures, Astellas, Bayer, Janssen-Cilag. H. Gurney: Travel reimbursement from Astellas and consultant/advisor for BMS, GSK, Pfizer, and Astellas. D.I. Quinn: Honoraria from Bayer, Astella, Novartis, Pfizer, Genentech/Roche, Merck, Merck Serono, Piramal, BMS, AstraZeneca, Dendreon, Exelixis, EMD Serono, and Sanofi and ad board acitivity from EMD Serono. Fees from a consulting or advisory role from Astellas Pharma, Novartis, Pfizer, BMS, Genentech/Roche, Merck Serono, Merck, Piramal, Bayer, Exelixis, AstraZeneca, Sanofi, Dendreon, and Peloton. Research funding from Millenium, Genentech/Roche, Sanofi, and GSK. S. Culine: Research funding from Astellas, Roche, and MSD and travel reimbursement from Amgen, Astellas, and Janssen, and served as consultant/advisor for Roche and Janssen. C.N. Sternberg: Personal fees from Oncogenex along with grants and personal fees from Lilly, Janssen, Merck, BMS, Astra Zeneca, and Roche Genentech. Y. Mai, M. Puhlmann: Employee of and own stock in Merck. R.F. Perini: Employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. In addition, Patent Application US 20160022814 A1 and 15101409 pending. J. Bellmunt: Honoraria from Merck, Genentech, Pfizer, and AstraZeneca. D.F. Bajorin: Research funding and travel reimbursement from Merck, Genentech, BMS, Roche, and Novartis, served as consultant/advisor for Merck, Genentech, Roche, Pfizer, AZ, and honoraria from Merck and Genentech.

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