An Up-To-Date Investigation Into the Correlation Between Proton Pump Inhibitor Use and the Clinical Efficacy of Immune Checkpoint Inhibitors in Advanced Solid Cancers: A Systematic Review and Meta-Analysis
Abstract
Background: Although immune checkpoint inhibitors (ICIs) have revolutionized the current anticancer therapies, a considerable proportion of patients are found to hardly benefit from these drugs. Accumulating studies have demonstrated that concomitant proton pump inhibitor (PPI) use may affect the clinical efficacy of ICIs; however, their results are inconsistent. In this study, based on updated evidence, we aimed to perform a meta-analysis to clarify the prognostic significance of PPI use in advanced solid cancer patients receiving ICI therapy.
Methods: Eligible literature was searched using PubMed, Cochrane Library, Web of Science, EMBASE, and other network resources before July 2021. Clinical outcome was evaluated using overall survival (OS) and progression-free survival (PFS). The correlation of PPI use with OS or PFS was determined based on hazard ratios (HRs) and 95% confidence intervals (CIs).
Results: A total of 17 studies enrolling 9,978 ICI-treated cancer patients were included in our meta-analysis. The global analysis demonstrated that PPI use was significantly correlated with worse OS [HR = 1.29 (1.10-1.50)] instead of PFS [HR = 1.19 (0.98-1.44)] in solid cancer patients receiving ICI therapy. In a subgroup analysis, the negative correlation of PPI use with ICI efficacy was significant in patients with non-small cell lung cancer [PFS, HR = 1.27 (1.10-1.47)] and urothelial carcinoma [OS, HR = 1.55 (1.31-1.84), PFS, HR = 1.52 (1.13-2.06)] and mixed cohorts…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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