Pembrolizumab offers a survival advantage and better safety profile compared with chemotherapy as second-line treatment of advanced urothelial carcinoma, according to researchers.

In an open-label, international phase 3 (KEYNOTE-045) trial, Joaquim Bellmunt, MD, PhD, and colleagues randomly assigned 542 patients with advanced urothelial carcinoma that recurred or progressed after platinum-based chemotherapy to receive either pembrolizumab or chemotherapy with paclitaxel, docetaxel, or vinflunine, at investigators’ discretion.

Pembrolizumab, which is a highly selective, humanized monoclonal antibody against programmed death 1 (PD-1), was administered at a dose of 200 mg every 3 weeks.

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The median overall survival was 10.3 months in the pembrolizumab group compared with 7.4 months in the chemotherapy group, the investigators reported in The New England Journal of Medicine (published online ahead of print). Compared with the chemotherapy group, pembrolizumab-treated patients had a significant 27% decreased risk of death.

In addition, the median overall survival among patients who had a tumor programmed death 1 ligand (PD-L1) combined positive score of 10% or more was 8.0 months in the pembrolizumab group versus 5.2 months in the chemotherapy group, a difference that corresponds to a significant 43% lower risk of death among the pembrolizumab recipients.

Dr Bellmunt’s group found no significant difference between the study arms in the duration of progression-free survival in the total population or among those who had a tumor PD-L1 combined positive score of 10% or more. A significantly smaller proportion of pembrolizumab than chemotherapy recipients reported treatment-related adverse events (60.9% vs 90.2%).

“The KEYNOTE-045 trial will have a practice-changing effect,” said Guru Sonpavde, MD, of the University of Alabama at Birmingham Comprehensive Cancer Center, in an accompanying editorial. “The longer survival and lower rates of toxic effects with pembrolizumab than with chemotherapy confer an improved therapeutic index in these generally elderly patients with coexisting conditions. As we celebrate the major advance that is provided by pembrolizumab, it is important to remember that this remains an incremental advance overall, although the responses were remarkably durable.”

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1. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 2017; published online ahead of print. doi: 10.1056/NEJMoa1613683

2. Sonpavde G. PD-1 and PD-L1 inhibitors as salvage therapy for urothelial carcinoma. N Engl J Med 2017; published online ahead of print. doi: 10.1056/NEJMe1701182