Efficacy and Safety of Immune Checkpoint Inhibitors Versus Chemotherapy in the Second-line Treatment of Advanced Esophageal Squamous Cell Carcinoma: a Meta-analysis and Systematic Review

Background: Esophageal cancer (EC) is the seventh most common cancer in the world, with 604,000 new cases diagnosed each year. Immune checkpoint inhibitors (ICIs) including programmed death ligand-1 (PD-L1) inhibitors have demonstrated a considerable survival advantage over chemotherapy in numerous randomized controlled trials (RCTs), particularly in patients with advanced esophageal squamous cell carcinoma (ESCC). In this analysis, we aimed to demonstrate that ICIs are more safe and effective than chemotherapy when used as a second-line treatment for advanced ESCC.

Methods: Publications on the safety and efficiency of ICIs in advanced ESCC that were available prior to February 2022 were searched in the Cochrane Library, Embase, and PubMed databases. Studies with missing data were eliminated, and studies that compared the treatments between the immunotherapy group and chemotherapy group were included. Statistical analysis was carried out using RevMan 5.3, and risk and quality were evaluated with relevant evaluation tools.

Results: Five studies met the inclusion criteria were selected, involving 1,970 patients with advanced ESCC. We compared chemotherapy and immunotherapy in the second-line treatment of advanced ESCC. ICIs considerably enhanced both the objective response rate (P=0.007) and overall survival (OS; P=0.001). However, the effect of ICIs on progression-free survival (PFS) was not significant (P=0.43). ICIs presented fewer grade 3-5 treatment-related adverse events (TRAEs), and there was also a suggested linkage between both PD-L1 expression and the effectiveness of the therapeutic intervention.

Conclusions: For patients with advanced ESCC, ICIs are more effective and safer than chemotherapy, and thus have a higher treatment value.