Current evidence of PD-1 and PD-L1 immune checkpoint inhibitors for esophageal cancer: an updated meta-analysis and synthesis of ongoing clinical trials

Background: Esophageal cancer (EC) is the sixth leading cause of cancer mortality worldwide, with a poor prognosis and a 5-year survival rate of 5% in advanced cases. Objectives: To evaluate the efficacy of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors in EC patients by analyzing phase III clinical trials. Design: A meta-analysis following the PRISMA Statement 2020 guidelines. Methods: PubMed/MEDLINE, Web of Science, and Embase were searched through 6 December 2022, and the analysis was conducted using Review Manager 5.4.3 (Cochrane). Results: Out of 387 studies, 13 phase III clinical trials with 6519 participants were pooled. Overall survival (OS) favored PD-1/PD-L1 inhibitors with a Cohen’s d of 0.28 (95% CI: 0.12–0.43; p = 0.0006), and the likelihood of achieving objective response also favored these inhibitors (OR: 2.04, 95% CI: 1.68–2.48; p < 0.0001). Conclusion: This meta-analysis provides strong evidence that PD-1/PD-L1 inhibitors combined with chemotherapy improve OS and objective response rate among patients with advanced EC but do not affect progression-free survival. Trial registration: Open Science Framework: osf.io/y27rx.