Meta-analysis of platinum chemotherapy combinations with immunotherapy in metastatic urothelial carcinoma

Abstract

The therapeutic landscape for metastatic urothelial carcinoma (mUC) has evolved significantly due to the development of innovative combination treatments, including enfortumab vedotin-pembrolizumab (EVP). Despite these advancements, the limited availability of EVP means that platinum-based chemotherapy regimens continue to serve as the primary treatment modality for many patients with mUC. We evaluated the effect of the type of platinum chemotherapy used in combination with immunotherapy (IO) on treatment outcomes in mUC. The meta-analysis showed that cisplatin-gemcitabine plus IO combination and carboplatin-gemcitabine plus IO combination improve progression-free survival compared to platinum-gemcitabine therapy (hazard ratio [HR] = 0.71, 95% CI: 0.62-0.82; P < .0001 and HR = 0.85, 95% CI: 0.73-0.98; P < .03, respectively). However, only the cisplatin-gemcitabine plus IO combination showed overall survival (OS) benefit (HR = 0.80, 95% CI: 0.69-0.93; P < .003). In comparison to the platinum-gemcitabine combination, neither the cisplatin-gemcitabine plus IO nor the carboplatin-gemcitabine plus IO combinations demonstrated an objective response rate (ORR) benefit. In summary, combining cisplatin-gemcitabine with immunotherapy offers significant overall survival benefits in mUC. The exact mechanisms—whether cisplatin’s immunomodulatory effects or patient demographic differences—are yet to be determined, necessitating further research to understand these outcomes better.