International immunopharmacologyNov 13, 2020

Proton pump inhibitor use linked to outcomes in patients treated with immune checkpoint inhibitors

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 29, 2026

Abstract

Analysis of seven studies revealed no significant association between proton pump inhibitor (PPI) use and overall survival (OS) or progression-free survival (PFS) in patients undergoing immune checkpoint inhibitor (ICI) therapy.

PPI use did not show a significant impact on overall survival (HR: 1.05, 95% CI: 0.79-1.40, P = 0.73).
No significant difference was found in progression-free survival for PPI users compared to non-users (HR: 0.90, 95% CI: 0.66-1.23, P = 0.51).
Subgroup analyses indicated that PPI use is associated with superior PFS in melanoma patients (HR: 0.50, 95% CI: 0.28-0.91, P = 0.02).
In contrast, PPI use was linked to inferior PFS in non-small cell lung cancer (NSCLC) patients (HR: 1.17, 95% CI: 1.05-1.31, P = 0.006).
The findings suggest that PPI therapy may benefit melanoma patients while potentially harming NSCLC patients undergoing ICI treatment.

Simplified

BACKGROUND: The 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.

METHODS: Searches 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).

RESULTS: A 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).

CONCLUSIONS: Our 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.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Proton pump inhibitor use linked to outcomes in patients treated with immune checkpoint inhibitors

Abstract

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