Comparison of Efficacy and Safety of First-Line Chemoimmunotherapy in Advanced Esophageal Squamous Cell Carcinoma: A Systematic Review and Network Meta-Analysis

Background. Chemoimmunotherapy has become the first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). We aimed to compare the efficacy and toxicity of different chemoimmunotherapy combinations to determine the optimal treatment option. Methods. PubMed, Web of Science, Cochrane Library, Embase, and abstracts of recent relevant meetings were searched to identify phase III randomized controlled trials (RCTs) of first-line programmed cell death-1 (PD-1)/its receptor (PD-L1) inhibitors plus chemotherapy for ESCC up to July 2022. A network meta-analysis (NMA) following Bayesian approaches was conducted in R software. Result. Our study included six RCTs and 3,611 patients. According to the NMA, toripalimab plus chemotherapy ranked first to prolong overall survival (OS). Sintilimab plus chemotherapy and camrelizumab plus chemotherapy consistently yielded the greatest benefits regarding progression-free survival (PFS). The maximal complete response rate (CRR) and objective response rate (ORR) were achieved with nivolumab plus chemotherapy. Tislelizumab plus chemotherapy attained the highest likelihood of achieving a disease control rate (DCR). The addition of immunotherapy to chemotherapy was associated with improved survival and increased adverse events. Subgroup analysis revealed that patients with PD-L1 tumor positive score (TPS) ≥10% showed a better OS than those with lower values when undergoing first-line chemoimmunotherapy. Anti-PD-1 inhibitor with platinum plus paclitaxel (TP) regimen showed a superior PFS benefit over anti-PD-1 inhibitor with platinum plus fluorouracil (FP) regimen. Conclusion. The NMA analysis suggested that sintilimab plus chemotherapy was the preferred regimen for treatment-naive advanced ESCC patients with the best balance between efficacy and safety. Anti-PD-1 inhibitors with the TP regimen were associated with more favorable PFS than those with the FP regimen.