Optimal first-line treatment for platinum-eligible metastatic urothelial carcinoma: Comparison of chemo-immunotherapy, immunotherapy, and chemotherapy- A systematic review and meta-analysis

Background: The role of first-line of immunotherapy in metastatic urothelial carcinoma (mUC) remains unclear. This meta-analysis aimed to explore an optimal first-line treatment strategy for mUC patients.Methods: We carried out a meta-analysis between chemo-immunotherapy, immunotherapy, and chemotherapy in mUC based on randomized trials. The outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.Results: Three trials involving 3238 patients were included. PD-1/PD-L1 inhibitor plus platinum-based chemotherapy was associated with the improvements of OS (HR, 0.85; 95% CI 0.75-0.99), PFS (HR, 0.80; 95% CI 0.71-0.90) and ORR (OR, 1.32; 95% CI 1.07-1.63) when compared with platinum-based chemotherapy, but not with better DCR (OR, 1.07; 95% CI 0.78-1.46). PD-1/PD-L1 inhibitor alone was associated with worse ORR (OR, 0.38; 95% CI 0.17-0.87) and DCR (OR, 0.20; 95% CI 0.16-0.25) when compared with platinum-based chemotherapy while it did not statistically reduce the risk of mortality (HR 0.97 for entire cohort; 0.90 for PD-L1 high cohort). In safety analyses, the incidence of adverse events (AEs) between regimens showed no difference, but the frequency of AEs of grade 3 or severity was higher in chemo-immunotherapy compared to chemotherapy.Conclusions: Compared with platinum-based chemotherapy, chemo-immunotherapy is associated with significantly improved PFS, OS, and ORR in the first-line therapy for mUC at the expanse of increased toxicity.