Startseite Kongressberichte 2017 ESMO 2017 Congress Urogenital Cancer Highlights Abstract LBA37_PR – ‘Pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine for recurrent, advanced urothelial cancer (UC): mature results from the phase 3 KEYNOTE-045 trial’

Mature results favour pembrolizumab as second-line treatment for bladder cancer

ESMO PRESS RELEASE LUGANO-MADRID, 10 September, 2017 – Mature results from the KEYNOTE-045 trial to be presented today at the ESMO 2017 Congress in Madrid (1) have confirmed significantly longer survival in patients with advanced urothelial cancer who receive the checkpoint inhibitor pembrolizumab after initial chemotherapy, compared to an alternative chemotherapy regimen.

The new data back up interim figures published earlier this year (2) and are “striking in the setting of urothelial cancer, which is highly lethal in the metastatic state,” said study investigator Dr Ronald de Wit, from Erasmus University Medical Center in Rotterdam, the Netherlands. 

“Pembrolizumab is the first agent to improve survival over chemotherapy in the second-line setting. Not all patients benefit from checkpoint inhibition, but a sizeable proportion of patients who respond have very durable responses, even well over one year,” noted de Wit.

The phase 3 study randomly assigned patients whose urothelial cancer had recurred or progressed after platinum-based chemotherapy, to either pembrolizumab (n=272) or the investigator’s choice of paclitaxel, docetaxel, or vinflunine chemotherapy (n=270).

Results now out after 22.5 months of follow-up show an approximately three month advantage in overall survival (OS) in the pembrolizumab-treated patients compared to those receiving a second-line of chemotherapy (median 10.3 months vs. 7.4 months), with a further improvement in the hazard ratio [HR] from 0.73 to 0.70 (P = 0.0003) since the interim analysis, he said.

Median progression-free survival (PFS) was not significantly different (2.1 months for pembrolizumab vs 3.3; HR, 0.96; P = 0.32).

“Some patients also benefit from second line chemotherapy, but these responses tend to be short-lived and toxicity typically prevents prolonged treatment, whereas pembrolizumab is well tolerated,” de Wit said, adding that treatment-related adverse events of any grade occurred in 62.0% of pembrolizumab-treated patients compared to 90.6% of those treated with chemotherapy.

In addition, quality of life (QOL), measured at week 15 and reported earlier this year, showed better results in the pembrolizumab arm. “Overall, the superior survival, better adverse event profile, and better QOL render pembrolizumab a new standard of care in the second line treatment of urothelial cell cancer,” he concluded.

Commenting on the study, Dr Maria De Santis, from the University of Warwick, Coventry, and Queen Elizabeth Hospital, Cancer Centre, in Birmingham, UK, said: “These updated KEYNOTE-045 results are important as they confirm the overall survival benefit of pembrolizumab compared to chemotherapy (investigator's choice) in platinum-pretreated patients. This is particularly important as the progression-free survival was not superior with pembrolizumab. The PFS curve in this trial diverges late but then, after 6 months, it was again in favour of pembrolizumab. As PFS does not seem to be a good surrogate endpoint with pembrolizumab, a confirmed, robust OS benefit as shown in this updated analysis becomes increasingly important. The robustness of the OS benefit is confirmed by the even better HR of 0.70 in this update, compared to 0.73 at the first presentation of the data last year.”

De Santis added that specific properties of this immunotherapy include “a superior duration of response in the 20% of patients who do respond and a favourable safety profile with a lower rate of severe side effects, compared to chemotherapy. Fewer patients on pembrolizumab had to discontinue treatment because of side effects compared to those on chemotherapy. Severe immune related side effects were rare. This is of special importance as patients with urothelial cancer are usually older with multiple comorbidities.”


Notes to Editors

Please make sure to use the official name of the meeting in your reports: ESMO 2017 Congress



1 Abstract LBA37_PR ‘Pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine for recurrent, advanced urothelial cancer (UC): mature results from the phase 3 KEYNOTE-045 trial’ will be presented by Dr Ronald de Wit during Poster Discussion Session ‘Genitourinary tumours, non-prostate’ on Sunday,10.09.2017, 14:45 - 16:15 (CEST), Cordoba Auditorium

2 N Engl J Med 2017;376:1015-26


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Abstract LBA37_PR – ‘Pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine for recurrent, advanced urothelial cancer (UC): mature results from the phase 3 KEYNOTE-045 trial’

R. de Wit1, D.J. Vaughn2, Y. Fradet3, J.-L. 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
1Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands, 2Medical Oncology, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA, 3Medical Oncology, CHU de Québec-Université Laval, Québec City, QC, Canada, 4Medical Oncology, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea, Republic of, 5Medical Oncology, University of California, San Francisco, San Francisco, CA, USA, 6Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA, 7Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia, Spain, 8Medical Oncology, Smilow Cancer Hospital at Yale University, New Haven, CT, USA, 9Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, 10Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, 11Medical oncology, Radboud University Medical Center, Nijmegen, Netherlands, 12Medical Oncology, Westmead Hospital and Macquarie University, Sydney, NSW, Australia, 13Medical Oncology, University of Southern California Norris Comprehensive Cancer Center and Hospital, Los Angeles, CA, USA, 14Medical Oncology, Hôpital Saint-Louis, Paris, France, 15Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy, 16Medical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA, 17Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, USA

Background: 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.

Methods: 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%.

Results: 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%.

Conclusions: 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., Kenilworth, NJ, USA

Funding: Merck & Co., Inc., Kenilworth, NJ, USA