Association of Immune-Related Adverse Events with Pembrolizumab Efficacy in the Treatment of Advanced Urothelial Carcinoma

Purpose: Immune-related adverse events (irAEs) have been associated with the efficacy of programmed cell death protein 1 (PD-1) inhibitors in patients with urothelial cancer. We therefore evaluated the relationship between irAEs and pembrolizumab efficacy in urothelial cancer patients. Methods: Patients with urothelial cancer who were treated with pembrolizumab in a second-line setting or later between January 2018 and December 2018 were identified by reviewing their medical records from the Cancer Institute Hospital, Japanese Foundation for Cancer Research. Data were updated as of December 31, 2018. Kaplan-Meier curves for overall survival (OS) and time to treatment failure (TTF) according to irAE grade were evaluated using the log-rank test. Risk factors for exacerbation of irAEs were also evaluated with multivariate analysis. Results: In this retrospective study, 43 patients received pembrolizumab. We identified irAEs in 22 of the 43 patients (51.2%), including 11 patients (25.6%) with grade 2 or 3 events. In patients with irAE grade 0 or 1, median TTF was 127 days, and median OS was 160 days according to the Kaplan-Meier method. On the other hand, in patients with irAE grade ≥2, median TTF and OS were not reached. Multivariate analysis also revealed that risk factors for exacerbation of irAEs (to grade ≥2) were positively associated with lymphocyte count at baseline (>2,000/µL) before pembrolizumab treatment (p = 0.021). Conclusions: Development of irAEs was associated with survival outcome of pembrolizumab treatment in patients with advanced urothelial cancer.