An evaluation of nivolumab plus gemcitabine and cisplatin in the treatment of advanced urothelial carcinoma.

Introduction: For decades, first-line treatment for advanced/metastatic urothelial cancer has been platinum-based chemotherapy. However, many patients do not respond to platinum-based chemotherapy alone, and the vast majority do not have durable responses. While immune checkpoint blockade has demonstrated benefit in this setting, initial trials of concurrent chemotherapy and immune checkpoint blockade did not demonstrate improvements in overall survival.

Areas covered: The recent CheckMate 901 trial compared gemcitabine, cisplatin, plus nivolumab to gemcitabine and cisplatin alone for first-line treatment of advanced/metastatic urothelial cancer. This was the first trial to demonstrate significant benefit in the combined chemotherapy and immune checkpoint blockade arm in advanced/metastatic urothelial cancer, most significantly showing an improvement in the primary outcomes of progression-free survival and overall survival, and the exploratory outcomes of objective response rate, complete response rate, and duration of complete response.

Expert opinion: The combination of gemcitabine, cisplatin, plus nivolumab represents a new first-line treatment option for metastatic urothelial cancer. This article details the clinical benefit observed and how this establishes proof-of-concept for prior hypotheses related to the importance of the specific chemotherapy regimen combined with immune checkpoint blockade, revolving around immunomodulatory mechanisms of action of cisplatin, and synergy of these mechanisms with immunotherapy.