ORLANDO Pembrolizumab following platinum-based chemotherapy was associated with significantly longer overall survival, fewer adverse events, and improved health-related quality of life compared with chemotherapy among patients with advanced urothelial carcinoma, according to findings presented at the 2017 Genitourinary Cancers Symposium.1

The international, open-label, phase 3 KEYNOTE-045 trial (ClinicalTrials.gov Identifier: NCT02256436) randomly assigned 542 patients with advanced urothelial cancer with recurrent or progressing disease following platinum-based chemotherapy to receive intravenous pembrolizumab or investigator’s choice of chemotherapy with paclitaxel, docetaxel, or vinflunine.

The efficacy and safety results, which were published in The New England Journal of Medicine, showed that median overall survival in the total population was 10.3 months (95% CI, 8.0-11.8) with PD-1 blockade compared with 7.4 months (95% CI, 6.1-8.3) with chemotherapy (hazard ratio [HR], 0.73; 95% CI, 0.59-0.91; P = .002).2

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Among those with a tumor PD-L1 combined positive score of 10% or greater, median overall survival was 8.0 months (95% CI, 5.0-12.3) in the pembrolizumab arm vs 5.2 months (95% CI, 0.37-0.88) in the chemotherapy arm (P = .005).

There were no significant differences in progression-free survival between the 2 treatment arms in the overall population (HR, 0.98; 95% CI, 0.81-1.19; P = .42) or in those with a tumor PD-L1 combined positive score of 10% or more (HR, 0.89; 95% CI, 0.61-1.28; P = .24).

Significantly fewer patients who received pembrolizumab had any grade treatment-related adverse events than those who received chemotherapy (60.9% vs 90.2%). There were also fewer grade 3 to 5 adverse events in the pembrolizumab arm (15.0% vs 49.4%).

Quality of life scores were stable for pembrolizumab-treated patients from baseline to week 15 but worsened for chemotherapy-treated patients. Patients in the pembrolizumab group without progressive disease had improved quality of life scores, whereas patients given chemotherapy had worsened scores.

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These findings support the use of pembrolizumab as second-line therapy for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy.


  1. Vaughn DJ, Bellmunt J, de Wit R, et al. Health-related quality of life (HRQoL) in the KEYNOTE-045 study of pembrolizumab versus investigator-choice chemotherapy for previously treated advanced urothelial cancer. Poster presented at: 2017 Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.
  2. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017 Feb 17. doi: 10.1056/NEJMoa1613683 [Epub ahead of print]