The effect of proton pump inhibitor uses on outcomes for cancer patients treated with immune checkpoint inhibitors: a meta-analysis

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for preventing and treating gastrointestinal ulcers. In patients with advanced cancer, it is unclear whether concomitant use of immune checkpoint inhibitors (ICIs) and PPIs could result in poorer outcomes. This study investigates the impact of PPIs on the survival of cancer patients treated with ICIs. METHODS: PubMed, MEDLINE, EMBASE, and the Cochrane Library databases were searched from January 1, 1970 to June 2, 2020 for studies reporting the prognoses of cancer patients receiving antitumor therapies including ICIs with or without PPIs. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Hazard ratios (HRs) with a 95% confidence interval (CI) were reported to express the effectiveness of ICIs in PPI users compared to non-PPI users, using a random effects model. RESULTS: Five studies were identified comprising 1,167 cancer patients. Concomitant use of PPIs with ICIs did not result in statistically significant changes in OS (HR 0.996; 95% CI: 0.486–1.447) and PFS (HR 0.858; 95% CI: 0.388–1.328). Statistical testing suggested heterogeneity among studies. Sensitivity analyses confirmed the stability of our results. CONCLUSIONS: Concomitant ICI-PPI therapy does not appear to be significantly associated with OS or PFS, and further research on the effect of individual ICIs in different cancer patients is needed.