The association between proton pump inhibitors use and clinical outcome of patients receiving immune checkpoint inhibitors therapy

Abstract

BackgroundThe gut microbiome can mediate the efficacy of immune checkpoint inhibitors (ICI). Meanwhile, proton pump inhibitors (PPI) can modulate the gut microbiome significantly. However, the impact of PPI use on the clinical outcome of ICI therapy remains unclear. MethodsSearches of PubMed, EMBASE, and the Cochrane Library were conducted to retrieve studies exploring the relationship between PPI use and the clinical benefit of patients undergoing ICI therapy through June 2020. The pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to evaluate the influence of PPI use on overall survival (OS) and progression-free survival (PFS). ResultsA total of seven studies were eligible for our final analysis. There was no significant association between PPI use and OS or PFS (PPI users versus non-users: HR for OS: 1.05, 95% CI: 0.79–1.40, P = 0.73; HR for PFS: 0.90, 95% CI: 0.66–1.23, P = 0.51). However, subgroup analyses demonstrated that PPI use was related to a superior PFS of melanoma patients (HR: 0.50, 95% CI: 0.28–0.91, P = 0.02) and an inferior PFS of non-small cell lung cancer (NSCLC) patients (HR: 1.17, 95% CI: 1.05–1.31, P = 0.006). ConclusionsOur present study indicates that PPI use is not significantly associated with OS and PFS of patients undergoing ICI treatment. However, concomitant PPI therapy may have a positive effect on melanoma patients and a negative effect on NSCLC patients. It is advisable for clinical oncologists to evaluate the necessity for PPI use when they treat patients with ICI therapy.