Efficacy and safety of immune checkpoint inhibitors for advanced or metastatic esophageal squamous cell carcinoma: A network meta-analysis

Abstract

Background: Combining immune checkpoint inhibitors (ICIs) with chemotherapy has significantly transformed cancer treatment, offering better options for esophageal squamous cell carcinoma (ESCC). This comprehensive network meta-analysis evaluates the efficacy and safety of various ICIs in patients with advanced ESCC.

Methods: A systematic literature search of randomized controlled trials (RCTs) was performed across major databases up to March 2025, focusing on studies comparing ICIs (as monotherapy or combined with chemotherapy) against chemotherapy alone. Efficacy and safety outcomes were synthesized using a frequentist network meta-analysis model to generate indirect and direct treatment comparisons.

Results: Thirteen trials involving 6997 patients revealed that combining ICIs with chemotherapy generally outperformed chemotherapy alone. Specifically, the combination of toripalimab and chemotherapy demonstrated the most significant improvement in overall survival (HR: 0.58, 95 % CI: 0.43-0.78, p = 0.0003; SUCRA: 0.86). Meanwhile, Sintilimab combined with chemotherapy provided the greatest benefit in progression-free survival (HR = 0.56, 95 % CI [0.46; 0.68], p-value <0.0001; SUCRA: 0.87). Tislelizumab alone was noted for its effectiveness in enhancing overall response rates (RR = 2.08, p = 0.0012). Nivolumab was the most effective in lowering the risk of grade 3 or greater adverse events compared to chemotherapy (RR = 0.28, 95 % CI: 0.21-0.39, p < 0.0001; SUCRA: 1).

Conclusion: Combining ICIs with chemotherapy revealed superior efficacy in advanced or metastatic ESCC compared to chemotherapy alone. These findings support using novel immunotherapeutic agents to enhance patient outcomes, warranting further research to optimize treatment regimens and manage adverse events effectively.

Keywords: Chemotherapy; Esophageal squamous cell carcinoma; Immune checkpoint inhibitors; Immunotherapy; Network meta-analysis.