Background: Immune checkpoint inhibitors (ICIs) are used in cancer immunotherapy; however, they can lead to immune-related adverse events (irAEs) through immune function of patients. Therefore, this meta-analysis aimed to assess the concomitant effect of acid suppressants (ASs) on ICIs, including several subgroup analyses.
Methods: We identified related studies and generated the forest plot. The primary endpoint was defined as the change in progression free survival (PFS) and overall survival (OS) with or without ASs administration. We also evaluated the effect of ASs on the incidence of irAEs.
Results: The total hazard ratio (HR) of ASs on PFS with ICI treatment was 1.39 and the 95% confidence interval (95% CI) was 1.21-1.59 (Z: p < 0.00001). Moreover, the total HR of ASs on OS was 1.40 and the 95% CI was 1.21-1.61 (Z: p < 0.00001), suggesting that ASs reduced ICI's therapeutic effect. The total odds ratio (OR) for evaluating the effect of ASs on irAEs was 1.23 with a 95% CI of 0.81-1.88 (Z: p = 0.34). However, ASs significantly worsened acute kidney injury (AKI) (total OR 2.10; 95% CI 1.74-2.53 (Z, p < 0.00001)). Furthermore, although proton pump inhibitors (PPIs) reduced ICI's therapeutic effect, histamine H2-receptor antagonists (H2RAs) did not affect OS.
Conclusions: It was shown that ASs, especially PPIs, reduced ICI's therapeutic effect, while H2RAs had no effect, and ASs did not affect irAEs; however, it is a risk factor for ICIs-induced AKI.
Keywords: Acid suppressant; Histamine H2-receptor antagonist; Immune checkpoint inhibitor; Immune-related adverse events; Proton pump inhibitor.
© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.