ESMO 2017: Pembrolizumab versus paclitaxel, docetaxel, or vinflunine for recurrent, advanced urothelial cancer: mature results from the phase 3 KEYNOTE-045 trial

Madrid, Spain ( Dr. De Wit and colleagues presented their late-breaking abstract this afternoon at ESMO 2017, reporting mature results from the phase III KEYNOTE-045 trial assessing pembrolizumab vs chemotherapy for patients with recurrent, advanced urothelial cancer. In the initial report of this trial, pembrolizumab was associated with significantly longer overall survival (OS) compared to either paclitaxel, docetaxel, or vinflunine chemotherapy (median 10.3 vs 7.4 months; HR 0.73, 95%CI 0.59-0.91) [1]. The objective of the current study was to present mature results from this phase III trial.

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. The primary end points were OS and progression free survival (PFS), and secondary end points included objective response rate (ORR) and safety. Treatment efficacy was assessed in all patients and patients with a PD-L1 combined positive score (% of PD-L1–expressing tumor and inflammatory cells) ≥10%. There were 270 patients assigned to pembrolizumab and 272 pts assigned to chemotherapy. Baseline characteristics were generally similar between arms. As of the follow-up cutoff of May 19, 2017, the median follow-up was 22.5 months for both treatment arms. Median OS was significantly longer with pembrolizumab vs chemotherapy in all patients (10.3 vs 7.4 months; HR, 0.70; p=0.0003) and in patients with a PD-L1 combined positive score ≥10% (8.0 vs 5.2 months; HR, 0.58; p=0.003). OS was longer with pembrolizumab vs chemotherapy regardless of age, liver metastases, hemoglobin, visceral disease, and choice of chemotherapy agent (as also reported in this session [2]). The 18-month OS rate was 33.2% (95%CI, 27.5-38.9) with pembrolizumab vs 19.7% (95%CI, 14.7-24.8) with chemotherapy. Median PFS was not significantly different between the two groups (2.1 vs 3.3 months; HR 0.96; p=0.32). ORR was 21.1% (95%CI, 16.4-26.5) for pembrolizumab and 11.0% (95%CI, 7.6-15.4) for patients treated with chemotherapy. Treatment-related adverse events of any grade occurred in 62.0% of patients treated with pembrolizumab and 90.6% treated with chemotherapy, including grade ≥3 treatment-related adverse events occurring in 16.5% and 50.2%, respectively.

With additional follow-up of KEYNOTE-045 patients, OS with pembrolizumab vs chemotherapy (paclitaxel, docetaxel, or vinflunine) continues to show significant differences (HR 0.70 vs 0.73 at first reporting - Sept 7, 2016). Additionally, pembrolizumab continues to have a superior safety profile compared with chemotherapy in patients with recurrent, advanced urothelial carcinoma.

Speaker: Ronald De Wit, Erasmus MC-Cancer Institute, Rotterdam, Netherlands

Co-Authors: : D. J. Vaughn (Philadelphia, United States of America) Y. Fradet (Québec City, Canada) J. Lee (Seoul, Korea, Republic of) L. Fong (San Francisco, United States of America) N. J. Vogelzang (Las Vegas, United States of America) M. A. Climent (Valencia, Spain) D. P. Petrylak (New Haven, United States of America) T. K. Choueiri (Boston, United States of America) 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) Y. Mai (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) D. F. Bajorin (New York, 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


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.
2. Petrylak D, Vogelzang NJ, Fradet Y, et al. Subgroup Analyses from KEYNOTE-045: Pembrolizumab versus Individual Investigator’s Choice of Chemotherapy (paclitaxel, docetaxel, or vinflunine) in Recurrent, Advance Urothelial Cancer. ESMO 2017 abstr 851.