Clinical benefit of continuing pembrolizumab treatment beyond progression in patients with metastatic urothelial carcinoma.

There has been no clinical evidence to justify continued pembrolizumab therapy beyond progression in patients with metastatic urothelial carcinoma (UC). We conducted a multicenter retrospective study evaluating the clinical efficacy of continued use of pembrolizumab beyond progression in patients with metastatic UC. Data from 51 patients with metastatic UC, who developed progression during second-line pembrolizumab therapy, were analyzed. Progression was defined based on the Immunotherapy Response Evaluation Criteria in Solid Tumors. The outcome was overall survival (OS). The association between continued treatment, OS, and the risk of all-cause mortality was tested using log-rank test, conventional and time-dependent Cox regression models. No significant difference in patient characteristics was noted between patients continuing pembrolizumab beyond progression (N = 21) and those discontinuing pembrolizumab (N = 30). Median OS was significantly longer in the continuation group (17.8 vs. 8.8 months; P = 0.038). A multivariable conventional Cox regression model identified continued pembrolizumab administration as a significant independent prognostic factor of all-cause mortality (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.05–0.90, P = 0.036), irrespective of the time from treatment initiation to progression and concurrent clinical progression. Further, longer duration of pembrolizumab treatment beyond progression was independently associated with a reduced risk of all-cause mortality in a multivariable time-dependent Cox regression model, when used as a time-dependent variable (HR: 0.07, 95% CI: 0.01–0.45, P = 0.006). Continued pembrolizumab administration beyond progression might be beneficial in patients with metastatic UC who were clinically stable.