Pembrolizumab in Combination With Gemcitabine and Concurrent Hypofractionated Radiation Therapy as Bladder-sparing Treatment for Muscle-invasive Urothelial Cancer of the Bladder: A Multicenter Phase 2 Trial.

[BACKGROUND AND OBJECTIVE] Trimodality therapy (TMT) is an accepted bladder-preserving option for selected patients with muscle-invasive bladder cancer (MIBC). Pembrolizumab has demonstrated activity in MIBC and may enhance the effects of chemotherapy and radiation. We evaluated the safety and efficacy of adding pembrolizumab to TMT.

[METHODS] In this multicenter phase 2 trial, patients with MIBC received one dose of pembrolizumab followed by maximal transurethral resection, then definitive bladder radiation with concurrent low-dose gemcitabine and pembrolizumab every 3 wk for three doses. The primary end point was 2-yr bladder-intact disease-free survival (BIDFS). Secondary end points included safety, metastasis-free survival (MFS), and overall survival (OS).

[KEY FINDINGS AND LIMITATIONS] Fifty-four patients were enrolled, including 48 in the efficacy cohort; 67% had clinical stage T2 disease. The 2-yr BIDFS was 60% (95% confidence interval [CI], 45-73). Two-yr MFS and OS were 81% (95% CI, 66-92) and 83% (95% CI, 69-91), respectively. Grade ≥3 treatment-related adverse events occurred in 25% of patients. Limitations include the single-arm design and modest sample size.

[CONCLUSIONS AND CLINICAL IMPLICATIONS] Pembrolizumab combined with gemcitabine-based chemoradiation was feasible and showed efficacy comparable to standard TMT. Ongoing phase 3 trials will further define its role in bladder preservation.