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Do proton pump inhibitors alter the response to immune checkpoint inhibitors in cancer patients? A meta-analysis

S. Lopes, L. Pabst, A. Dory, Marion Klotz, B. Gourieux, B. Michel, C. Mascaux

Frontiers in Immunology, 2023

20,042 participants · 74 citations

Abstract

Introduction: Gut microbiota can significantly affect the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. Recently, antibiotics were shown to decrease survival rate of patients treated by ICIs. Proton pump inhibitors (PPIs) can indeed modulate microbiota's diversity, therefore altering ICIs response. A meta-analysis was performed based on published data to verify this hypothesis.

Methods: In this study, over 41 publications, exploring the impact of concomitant PPI treatment on outcomes of ICI-treated patients, were analyzed. Evaluated endpoints were overall survival (OS) and progression-free survival (PFS). Pooled hazard ratios (HRs) with a 95% confidence interval (CI) were reported in ICIs in PPI users versus non-PPI users. Subgroup analyses were performed to minimize the impact of study heterogeneity and to investigate the influence of PPI on the different groups of interest. There was no evidence of publication bias for OS and PFS analysis in subgroup analysis.

Results: Forty-one studies were included in the meta-analysis, including a total of 20,042 patients. OS of patients receiving ICIs was negatively correlated in patients concomitantly treated with PPI (HR=1.37; 95%CI, 1.23-1.52). PFS of cancer patients receiving ICIs was also negatively correlated with PPI treatment (HR=1.28; 95%CI, 1.15-1.42). PPI and ICI use was associated with worst OS and PFS not only for non-small-cell lung cancer (NSCLC) or urothelial cancer patients but also for…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 20,042 participants or records.

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