Multinational phase 3 trial of perioperative durvalumab with neoadjuvant chemotherapy in operable muscle-invasive bladder cancer

Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC). Adding perioperative immunotherapy may improve outcomes. The multinational phase 3 NIAGARA trial evaluated perioperative durvalumab with neoadjuvant chemotherapy for cisplatin-ineligible patients with MIBC. Patients were randomized 1:1 to neoadjuvant durvalumab plus gemcitabine-cisplatin chemotherapy every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group; n=533) or neoadjuvant gemcitabine-cisplatin followed by radical cystectomy (comparison group; n=530).The event-free survival rate at 24 months (primary endpoint) was 67.8% in the durvalumab group and 59.8% in the comparison group (HR 0.68; p<0.001). The overall survival rate at 24 months (secondary endpoint) was 82.2% in the durvalumab group and 75.2% in the comparison group (HR 0.75; p=0.01). Treatment-related adverse events of grade 3 or 4 occurred in 40.6% of patients in the durvalumab group and 40.9% of patients in the comparison group; TRAEs of grade 5 occurred in 0.6% in both groups. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of the patients in the comparison group. The authors conclude that perioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherapy alone in cisplatin-ineligible patients with MIBC.