Second-Line Therapy for Advanced Urothelial Cancer

Treatment options are limited and prognosis is poor for patients with advanced urothelial cancer who relapse after receiving standard platinum-based chemotherapy. During the past year, two checkpoint inhibitors — atezolizumab, a programmed death 1 ligand (PD-L1) inhibitor, and nivolumab, a programmed death 1 (PD-1) inhibitor — received FDA-accelerated approval for use in such patients, based on objective-response results from large, single-arm, phase II trials.

Now, international investigators have conducted an industry-supported, randomized, open-label, phase III trial to evaluate the use of the PD-L1 inhibitor pembrolizumab in patients with previously treated advanced disease. A total of 542 patients received either pembrolizumab or chemotherapy with paclitaxel, docetaxel, or vinflunine. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS).

Median OS was longer with pembrolizumab versus chemotherapy (10.3 vs. 7.4 months; hazard ratio for death, 0.73; P=0.002); however, median PFS was similar with both treatments (2.1 and 3.3 months, respectively). The overall objective response rate was higher with pembrolizumab (21.1% vs. 11.4%). Serious adverse events were less common with pembrolizumab (15.0% vs. 49.4%).