Clinical evidence of neoadjuvant immunotherapy for resectable locally advanced esophageal carcinoma: A systematic review

Background: Immune checkpoint inhibitors (ICIs) as the neoadjuvant therapy for resectable locally advanced esophageal carcinoma (rlaEC) remains challenging given the poor reports of efficacy and safety. This study aimed to summarize reliable evidence for the preoperative neoadjuvant immunotherapy of rlaEC by analyzing all the published clinical trials on the ICIs as the neoadjuvant therapy for rlaEC. Methods: PubMed, Cochrane Library, Embase and ClinicalTrials.gov were searched from inception until June 1st, 2023, for available reports to perform a meta-analysis. The primary endpoints were R0 resection, objective response rate (ORR), pathological complete response (pCR) and major pathological response (MPR), as well as treatment-related adverse events (AEs) and postoperative complications. The Stata 14.0 software was employed to estimate pooled effect size. Results: A total of 18 single-arm clinical trials involving 625 patients met the inclusion criteria. Meta-analysis showed that, among these patients with rlaEC, the pooled R0 resection rate was 97.0% (95% CI: 94.0% – 99.0%), the pooled ORR was 70.0% (95% CI: 64.0% – 76.0%), the pooled pCR and MPR rate were 34.0% (95 % CI: 29.0% – 39.0%) and 56.0% (95% CI: 47.0% – 65.0%) respectively. The incidence of main treatment-related AEs and postoperative complications was about 6% – 45% and 8% – 19% respectively. Conclusions: Patients with rlaEC were tolerated to neoadjuvant immunotherapy and it might be beneficial to improve efficacy. But this meta-analysis had limitations and the conclusions still needed to be validated by more rigorous phase III randomized controlled clinical trials.