Efficacy and safety of first-line immunotherapy-containing regimens compared with chemotherapy for advanced or metastatic urothelial carcinoma: a network meta-analysis of randomized controlled trials

Introduction: To assess the efficacy and safety of first-line immunotherapy-containing regimens compared with chemotherapy for advanced or metastatic urothelial carcinoma (UC).

Method: A comprehensive search was performed in four databases (Pubmed, Embase, Web of Science, and the Cochrane Library) to identify randomized controlled trials (RCTs) assessing the efficacy of first-line immunotherapy-containing regimens for advanced or metastatic UC. The search encompassed the time span from the inception of the databases to April 23, 2024. A network meta-analysis (NMA) was conducted to assess the rates of progression-free survival (PFS), overall survival (OS), complete response (CR), objective response rate (ORR), and grade ≥ 3 adverse events (AEs).

Results: We conducted a comprehensive analysis of five randomized controlled trials (RCTs) that included a total of 4749 patients. Nine different treatment regimens included in the study were ranked statistically and intuitively using NMA. The top five effective regimens, ranked by OS, were EV + Pembro (1.000), Nivol + Chemo (0.724), Atezo + Chemo (0.610), Durva + Treme (0.558), and Pembro + Chemo (0.530). The top five effective regimens, ranked by PFS, were EV + Pembro (0.999), Nivol + Chemo (0.640), Pembro + Chemo (0.484), Atezo + Chemo (0.373) and Chemo (0.003). The top five effective regimens, ranked by CR, were EV + Pembro (0.969), Nivol + Chemo (0.803), Atezo + Chemo (0.772), Pembro + Chemo (0.472), Durva + Treme (0.449). The top five effective regimens, ranked by ORR, were EV + Pembro (0.995), Nivol + Chemo (0.852), Pembro + Chemo (0.761), Atezo + Chemo (0.623), and Chemo (0.519).

Conclusion: Our results indicated that EV + Pembro as first-line therapy resulted in considerably improved efficacy and safety compared to chemotherapy for advanced or metastatic UC. ICI plus chemotherapy as first-line treatment resulted in a longer PFS, a greater ORR, but no longer OS compared to chemotherapy alone, as well as higher toxicity. ICI alone as first-line therapy provided similar OS and lower toxicity compared to chemotherapy, but lower ORR.

Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024538546.