Proton pump inhibitor use and overall survival in patients with gastric adenocarcinoma treated with first-line immunotherapy: A real-world pharmacoepidemiologic study
Abstract
e15693
Background:
Proton pump inhibitors (PPIs) are frequently prescribed to patients with gastric cancer for gastroesophageal reflux disease (GERD), ulcer prophylaxis, and symptom control. Emerging evidence suggests that PPIs may adversely affect immune checkpoint inhibitor (ICI) efficacy by disrupting gut microbiota composition, a factor increasingly recognized as a determinant of the antitumor immune response. We evaluated the association between concomitant PPI use and overall survival (OS) in a real-world cohort of patients receiving first-line ICI therapy.
Methods:
We performed a retrospective study using TriNetX. Adult patients with gastric adenocarcinoma who initiated nivolumab- or pembrolizumab-based first-line treatment between 2016 and 2024 were identified. Patients were classified as active PPI users if they had documented PPI prescription/administration (omeprazole, pantoprazole, esomeprazole, lansoprazole) within 30 days before or after ICI initiation, and non-users otherwise. Cohorts were 1:1 propensity score-matched for age, sex, PPI indication, comorbidities, baseline corticosteroid use, and prior Helicobacter pylori infection. OS was analyzed using Kaplan–Meier and Cox proportional hazards models. Sensitivity analyses exclude patients with recent GI bleeding and restricted exposure to sustained PPI use (> 60 days).
Results:
Following propensity score matching, 4,372 patients were included (2,186 PPI users and 2,186 non-users). Baseline characteristics were…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 4,372 participants or records.
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