Platinum-based chemotherapy for first-line treatment of metastatic urothelial cancer is typically administered for a fixed duration followed by observation. Previous research indicates that pembrolizumab improves survival of metastatic urothelial cancer that has progressed following platinum-based chemotherapy. Researchers assessed the potential benefit of earlier pembrolizumab using a “switch maintenance” approach and found that this may “deepen responses achieved with first-line chemotherapy.” The results of the multi-institutional, randomized, placebo-controlled, double-blind, phase II study were presented at the 2019 ASCO Annual Meeting.
Researchers enrolled patients with metastatic urothelial cancer who achieved at least stable disease (SD) after up to eight cycles of first-line platinum-based chemotherapy. Between December 2015 and November 2018, 107 patients were randomized 1:1 to receive pembrolizumab 200 mg intravenously every three weeks (n=55; median age = 68 years; range = 41-83 years) or placebo (n=52; median age = 65 years; range = 44-87 years) for up to 24 months. Patients receiving placebo could cross over to receive pembrolizumab. Patients were stratified based on pre-chemotherapy visceral metastases (yes vs. no) and response to first-line chemotherapy (complete response (CR)/partial response (PR) vs. SD).
Most patients in both cohorts received cisplatin-based first-line chemotherapy: 39 patients (71%) in the pembrolizumab cohort and 41 (79%) in the placebo cohort. Most patients in both groups achieved a CR or PR to previous first-line therapy: 40 patients (73%) in the pembrolizumab group and 36 (69%) in the placebo group.
Patients received a median of six cycles of placebo and eight cycles of pembrolizumab. When researchers excluded patients with a CR at baseline, the objective response rate was 12% (n=5/42) with placebo and 22% (n=10/46) with pembrolizumab.
Grade 3/4 treatment-related adverse events occurred in 48% of patients receiving placebo and 56% of patients receiving pembrolizumab. At a median follow-up of 14.7 months, 41 patients died and 26 patients in the placebo cohort crossed over to receive pembrolizumab.
Progression-free survival (PFS; primary endpoint) was significantly longer in patients receiving pembrolizumab versus placebo (P=0.038). The 18-month restricted mean PFS was 5.6 months with placebo and 8.2 months with pembrolizumab (P=0.023).
Galsky MD, Pal SK, Mortazavi A, et al. Randomized double-blind phase II study of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients (pts) with metastatic urothelial cancer (mUC): HCRN GU14-182. Abstract #4504. Presented at the 2019 ASCO Annual Meeting, Chicago, IL, June 3, 2019.