Safety and efficacy of sintilimab-based neoadjuvant immunochemotherapy for resectable esophageal squamous cell carcinoma: A pooled analysis

Background Sintilimab, a fully human IgG4 monoclonal antibody that targets the programmed cell death receptor-1 (PD-1), blocks the interaction of PD-1 with its ligands, PD-L1 and PD-L2, thereby aiding in the restoration of the endogenous antitumor T-cell response. Although clinical trials for sintilimab-based neoadjuvant immunochemotherapy (sintilimab-based nICT) in resectable esophageal squamous cell carcinoma (ESCC) are increasing, comprehensive evaluations remain scarce. Methods PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were searched for eligible studies up to May 30, 2024. The estimated outcomes were pathological complete response (pCR),major pathological response (MPR), objective response rate (ORR), disease control rate (DCR), complete remission (CR), partial remission (PR), stable disease (SD), and disease progression (PD),, TNM and N down-degrading rate, R0 surgical resection grade 3 or higher treatment-related adverse events(TRAEs ≥ 3), and anastomotic leakage(AL), disease free survival (DFS), and overall survival(OS). A random-effects model was used to integrate the pooled rate when heterogeneity was present. Results A total of 14 studies, involving 652 patients with resectable ESCC, were enrolled. The pooled rates were as follows: 27% (95% CI, 23%-30%) for pCR, 45% (95% CI, 36%-54%) for MPR, 65% (95% CI, 46%-82%) for ORR, 99% (95% CI, 96%-100%) for DCR, 18% (95% CI, 9%-25%) for CR, 53% (95% CI, 35%-71%) for PR, 32% (95% CI, 16%-51%) for SD, 1% (95% CI, 0%-3%) for PD, 87% (95% CI, 71%-97%) for one-year DFS, 94% (95% CI, 85%-99%) for one-year OS, 89% (95% CI, 84%-93%) for two-year OS, 69% (95% CI, 59%-79%) for TNM down-degrading, 67% (95% CI, 52%-82%) for N down-degrading, 98%(95% CI, 93%-100%) for R0 surgical resection,19% (95% CI, 13%-26%) for TRAEs ≥ 3,and 7% (95% CI, 4%-9%) for AL . Conclusions Sintilimab-based nICT exhibits a safe and efficacious profile for the treatment of resectable ESCC.