ESMO 2017: KEYNOTE-045: Pembrolizumab vs Individual Investigator’s Choice of Chemotherapy in Recurrent, Advanced Urothelial Cancer

Madrid, Spain ( Dr. Petrylak and colleagues presented their subgroup analysis of KEYNOTE-045 assessing pembrolizumab vs individual chemotherapy agents for patients with recurrent, advanced urothelial carcinoma. In the phase III KEYNOTE-045 study, overall survival (OS) was significantly longer with pembrolizumab vs investigator’s choice of chemotherapy regimen (median 10.3 vs 7.4 months; HR 0.73, 95%CI 0.59-0.91) [1]. The objective of this post-hoc analysis was to assess the outcomes of patients treated with pembrolizumab to the individual agents in the chemotherapy arm. 

There were 525 patients included in the analysis, including 270 treated with pembrolizumab, 84 with paclitaxel, 84 with docetaxel, and 87 with vinflunine. Inclusion criteria included patients with (i) histologically or cytologically confirmed urothelial carcinoma, (ii) progression after platinum, (iii) ECOG performance status 0-2, (iv) measurable disease (RECIST v1.1), and (v) ≤2 lines of systemic therapy received. These patients were then randomly assigned 1:1 to pembrolizumab 200 mg Q3W or the investigator’s choice of paclitaxel 175 mg/m2 Q3W, docetaxel 75 mg/m2 Q3W, or vinflunine 320 mg/m2 Q3W. Primary end points included OS and PFS (RECIST v1.1, blinded central review), and ORR (RECIST v1.1, blinded central review) was a secondary end point. Baseline demographics were well balanced among the groups, and median follow-up was 14 months (range, 10-22 months). Pembrolizumab 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 pembrolizumab and each of the chemo agents. ORR (95% CI) was 21% (16%-27%) with pembrolizumab vs 12% (6%-21%) for paclitaxel, vs 6% (2%-13%) for docetaxel, and vs 18% (11%-28%) for vinflunine. Treatment-related adverse events occurred in 61% (pembrolizumab), 88% (paclitaxel), 92% (docetaxel), and 91% (vinflunine) of patients. Treatment-related adverse events of grade ≥3 severity included 15% (pembrolizumab), 44% (paclitaxel), 54% (docetaxel), and 51% (vinflunine).

In conclusion, in this subgroup analysis of patients in the KEYNOTE-045 trial, pembrolizumab was associated with longer OS, higher antitumor activity, and lower incidence of toxicities than single-agent paclitaxel, docetaxel, or vinflunine in patients with advanced urothelial carcinoma. Pembrolizumab is the first agent to demonstrate OS improvement vs chemotherapy in this setting and should be considered for use in recurrent, advanced urothelial carcinomas.


1. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017;376(11):1015-1026.

Speaker: Daniel Petrylak, Yale Comprehensive Cancer Center, New Haven, United States of America

Co-Authors: N. J. Vogelzang (Las Vegas, United States of America) Y. Fradet (Quebec City, Canada) D. Bajorin (New York, United States of America) R. De Wit (Rotterdam, Netherlands) D. J. Vaughn (Philadelphia, United States of America) J. Lee (Seoul, Korea, Republic of) L. Fong (San Francisco, United States of America) M. A. Climent (Valencia, Spain) A. Necchi (Milan, Italy) W. R. Gerritsen (Nijmegen, Netherlands) H. Gurney (Sydney, Australia) D. I. Quinn (los angeles, United States of America) S. Culine (Paris, France) C. N. Sternberg (Rome, Italy) E. Jensen (Kenilworth, United States of America) M. Puhlmann (Kenilworth, United States of America) R. F. Perini (Kenilworth, United States of America) J. Bellmunt (Boston, United States of America) T. K. Choueiri (Boston, United States of America)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain