A Systematic Review and Meta-analysis of PD-1 and PD-L1 Inhibitors Monotherapy in Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma

摘要

Immune checkpoint inhibitors are new targeted treatments that harness the body's immune system to attack cancers. Drugs that are most extensively used among checkpoint inhibitors inhibit the PD-L1 or PD-1 (programmed death 1) ligand or receptor pair and are currently approved for many cancer indications. In gastric or gastroesophageal junction adenocarcinomas one inhibitor, pembrolizumab has regulatory approval for PD-L1 positive carcinomas. This meta-analysis investigates available data on the efficacy of PD-L1 or PD-1 inhibitors as a class in gastric or gastroesophageal junction adenocarcinomas. The literature was reviewed to identify clinical studies that included arms with PD-L1 or PD-1 inhibitors as monotherapy in gastric or gastroesophageal junction adenocarcinomas. Relevant patient characteristics, outcomes, and adverse effects were recorded. Summary estimates of response rates (RR) and survival were calculated using a random or fixed effect model, depending on heterogeneity. Six studies with a total of 1068 patients were included in the analysis. The summary RR was 10.63% (95% confidence interval (CI) 5.36–15.89%). The summary disease control rate (DCR) was 28.11% (95% CI 24.60–31.63%). Summary progression-free survival (PFS) was 1.59 months (95% CI 1.24–1.94 months). Summary overall survival (OS) was 5.72 months (95% CI 0–12.19 months). A subset of patients derived long-term benefits as seen in other cancer locations. The adverse effect rate was low and consistent with that in other disease locations. Low efficacy of immune checkpoint inhibitors as a class in gastric or gastroesophageal junction adenocarcinomas is observed in this analysis and stresses the need for effective biomarker use for the identification of most probable responders.