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.