Second-line treatment with pembrolizumab significantly improved overall survival compared with chemotherapy among patients with advanced urothelial carcinoma who received first-line platinum-based chemotherapy, according to a study presented at the European Cancer Congress (ECCO) 2017.1

The open-label, phase 3 KEYNOTE-045 trial ( Identifier: NCT02256436) enrolled 270 patients with recurrent or progressive metastatic urothelial carcinoma regardless of PD-L1 expression. The patients were randomly assigned 1:1 to receive intravenous pembrolizumab every 3 weeks for 24 months or investigator’s choice of paclitaxel, docetaxel, or vinflunine every 3 weeks.

Results showed that pembrolizumab therapy reduced the risk of death by about 28% compared with investigator’s choice of chemotherapy (hazard ratio [HR], 0.723; 95% CI, 0.59-0.91; P < .0022). Median overall survival with pembrolizumab was 10.3 months (95% CI, 8.0-11.8) vs 7.4 months (95% CI, 6.1-8.3) with chemotherapy; the 1-year overall survival rates were 43.9% and 30.7%, respectively.

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More than 20% of pembrolizumab-treated patients achieved a confirmed objective response, including complete responses in 7%.

There was, however, no statistically significant difference in progression-free survival between the 2 treatment arms (HR, 0.98; 95% CI, 0.81-1.19; P = .42).

RELATED: Nivolumab Active Regardless of PD-L1 Expression in Advanced Urothelial Carcinoma

Pembrolizumab was also associated with fewer any-grade and grade 3 to 4 treatment-related adverse events. The most common treatment-related adverse events in the pembrolizumab arm were pruritus, fatigue, nausea, and diarrhea.

Four patients in each arm died from treatment.


  1. Necchi A, Bellmunt J, de Wit R, et al. Pembrolizumab vs investigator-choice chemotherapy for previously treated advanced urothelial cancer: phase 3 KEYNOTE-045 study. Paper presented at: European Cancer Congress 2017; January 27-30, 2017; Amsterdam, Netherlands.