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Proton Pump Inhibitor Use and Survival in Patients With Newly Diagnosed Glioblastoma

Le Rhun E, Sain D, Erridge SC, Reardon DA, Minniti G, Roth P, Wick W, Nabors B et al.

JAMA network open, 2025

2,981 participants · 2 citations

Abstract

Importance: Proton pump inhibitors (PPI) are often prescribed to prevent steroid-induced gastritis and peptic ulcer disease in patients with glioblastoma. Yet, these drugs may enhance the activity of aldehyde dehydrogenase 1 A1 (ALDH1A1), which has been linked to protection from oxidative stress, radiotherapy, and chemotherapy.

Objective: To explore the associations of the use of potent ALDH1A1-activating PPIs (PA-PPIs) and other antacid drugs with outcomes in patients with newly diagnosed glioblastoma.

Design, setting, and participants: This meta-analysis was a secondary analysis of individual prospectively captured patient data using a dataset of 5 randomized clinical trials conducted between 2008 and 2020. Participants included patients with a new diagnosis of glioblastoma. Data analysis was completed in November 2024.

Exposure: We assessed drug use at baseline and defined 3 landmarks: start of temozolomide maintenance cycles 1 (landmark 1) and 4 (landmark 2), and end of cycle 6 (landmark 3).

Main outcomes and measures: The primary outcome measures were progression-free survival (PFS) and overall survival (OS) from baseline and from the start of each corresponding landmark time.

Results: The study population included 2981 patients (1858 [62.3%] male; median [range] age, 58 [18-85] years). On univariate analysis, patients treated with PA-PPI had worse PFS and OS at all 4 time points. The multivariate analysis accounting for age, sex, performance status, steroid use, extent…

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: 2,981 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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