Compared in a phase 3 trial with gemcitabine–cisplatin in patients with untreated unresectable or metastatic urothelial carcinoma, nivolumab plus gemcitabine–cisplatin resulted in significantly better outcomes, researchers report. The improvements included “deep and durable responses” the authors conclude, and “our findings provide evidence of the benefit of concurrent administration of an immune checkpoint inhibitor and chemotherapy in improving survival in this population.”
The multinational, open-label trial randomized 608 participants to intravenous nivolumab 360 mg plus gemcitabine–cisplatin (nivolumab combination) every 3 weeks for up to 6 cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine–cisplatin alone every 3 weeks for up to 6 cycles. Based on primary outcomes of overall and progression-free survival, the investigators found: “At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine–cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P = 0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine–cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P = 0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine–cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine–cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively.”