Efficacy and Safety Profile of PD-1 Inhibitors Versus Chemotherapy in the Second-line Treatment of Advanced Esophageal Squamous Cell Carcinoma: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Purpose: PD-1 inhibitors have emerged as the new standard of care for second-line treatment of advanced esophageal squamous cell carcinoma. There have been lots of research lately concerning the topic. A comprehensive assessment of the efficacy and safety profile between PD-1 inhibitors and chemotherapy is warranted. Methods: : PubMed, Embase, Cochrane Library, and Embase were searched systematically until May 1 st , 2022. We extracted data on efficacy and safety and calculated the pooled HRs and RRs with 95%CI using randomized-effect or fixed-effect models. A subgroup analysis was applied to explore the factors modifying the response to PD-1 inhibitors. All data were statistically analyzed by R 4.1.2. Results: : A total of 5 studies involving 1,970 patients were included in our meta-analysis. PD-1 inhibitors group could attain greater overall survival benefit (HR = 0.73, 95%CI 0.66-0.81, P < 0.001) and nearly favorable progression-free survival (HR = 0.89, 0.76-1.04, P = 0.13). TRAEs (RR = 0.76, 95%CI 0.64-0.91, P = 0.004) and level 3-5 TRAEs (RR = 0.40, 95%CI 0.32-0.49, P < 0.001) were significantly diminished in PD-1 inhibitors groups. Among all modifying factors, PD-L1 combined positive score was positively associated with the patient’s overall survival. Conclusions: : This analysis suggests that PD-1 inhibitors exhibited better survival outcomes and safety profiles than standard-of-care chemotherapy. High levels of PD-L1 combined positive scores was associated with an enhanced response to PD-1 immunotherapies with regard to overall survival.