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.