Efficacy and safety of PD-1/PD-L1 inhibitors as first-line treatment for esophageal squamous cell carcinoma: a systematic review and meta-analysis.

Purpose: This study aims to investigate the efficacy and safety of PD-1/PD-L1 inhibitors in the first-line treatment of esophageal squamous cell carcinoma (ESCC) and identify factors influencing efficacy through a meta-analysis of multiple phase 3 randomized controlled trials (RCTs). Methods: A systematic literature search was conducted in Cochrane, PubMed, and Embase databases. Two researchers independently extracted trial data, including efficacy-related outcomes such as overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR), along with their subgroup data and safety-related indicators. The overall hazard ratio (HR) and 95% confidence interval (CI) were calculated for OS and PFS, while the overall odds ratio (OR) and 95% CI were computed for ORR to compare the classification and predictive abilities of combined positive score (CPS) and tumor proportion score (TPS) for PD-L1 status. Additionally, survival outcomes across different subgroups were evaluated to explore the potential influencing factors for the efficacy of PD-1/PD-L1 inhibitors in ESCC. Results: This meta-analysis included eight phase 3 RCTs encompassing 4,479 participants. PD-1/PD-L1 inhibitors combined with chemotherapy significantly improved OS ( Conclusions: This study confirms that the combination of PD-1/PD-L1 inhibitors and chemotherapy provides significant clinical benefits in ESCC. CPS =10 serves as a key threshold for predicting treatment response. There is a trend suggesting that male, Asian, smoking, and liver metastasis patients may experience better survival benefits, while no significant difference was observed between TP- and FP-based regimens. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024536221.