PD‐1/L1 inhibitors can improve but not replace chemotherapy for advanced urothelial carcinoma: A systematic review and network meta‐analysis.

Background: Programmed cell death‐1/ligand 1 inhibitors are a new treatment strategy for advanced urothelial carcinoma. Therefore, a comparative evaluation of their efficacy and toxicity compared with chemotherapy is necessary. Methods: We comprehensively searched PubMed, Web of Science, Embase, and Cochrane Library databases and performed a meta‐analysis of randomized controlled trials up to July 2021. We considered overall survival as the primary outcome, and progression‐free survival, objective response rate, and treatment‐related adverse events as secondary outcomes. Results: Overall, 3584 patients from five studies were evaluated. Compared with first‐line chemotherapy, programmed cell death‐1/ligand 1 inhibitors were significantly associated with worse progression‐free survival (p < 0.001) and adverse objective response rates (p < 0.001). However, the treatments were not significantly different in terms of overall survival (p = 0.33). Compared with second‐line chemotherapy, programmed cell death‐1/ligand 1 inhibitors significantly improved overall survival (p < 0.001), and there was no statistically significant difference in progression‐free survival (p = 0.89) or objective response rate (p = 0.34). Compared with chemotherapy, programmed cell death‐1/ligand 1 inhibitors were well tolerated (first‐line chemotherapy: p < 0.001; second‐line chemotherapy: p < 0.001). Conclusions: The efficacy of programmed cell death‐1/ligand 1 inhibitors in patients with advanced urothelial carcinoma is not superior to that of first‐line platinum‐based chemotherapy but is better than second‐line chemotherapy; however, programmed cell death‐1/ligand 1 inhibitors are safer than first‐ and second‐line chemotherapy and have a broader prospect for use in combination therapy. [ABSTRACT FROM AUTHOR]