TOPLINE:

Use of certain proton pump inhibitors (PPIs) was associated with worse progression-free and overall survival in patients with newly diagnosed glioblastoma, according to findings from a meta-analysis.

METHODOLOGY:

• PPIs are often prescribed to prevent steroid-related gastric complications during glioblastoma care, but some PPIs activate aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), a protein linked to cellular protection and treatment resistance.
• To understand how PPI use might affect survival outcomes among patients receiving treatment for glioblastoma, researchers conducted a meta-analysis of patient data from five randomized clinical trials, which included 2981 patients with newly diagnosed glioblastoma (median age, 58 years; 62.3% male).
• Drugs altering gastric pH were categorized as PPIs that were potent activators of ALDH1A1 (PA-PPIs), such as omeprazole and pantoprazole. The use of PPIs was assessed at baseline and at three treatment timepoints: 70 days later (at the start of temozolomide maintenance cycle 1), 84 days later (at the start of maintenance cycle 4), and an additional 84 days later (at the end of maintenance cycle 6).
• Researchers determined progression-free survival and overall survival from baseline and from the start of each corresponding timepoint.
• The multivariate analysis accounted for age, sex, performance status, steroid use, extent of resection, and MGMT promoter methylation status.

TAKEAWAY:

• Use of PA-PPI was associated with significantly worse progression-free survival at each timepoint — first (hazard ratio [HR], 1.14), second (HR, 1.26), and third (HR, 1.31). Use of PPIs was also associated with significantly worse overall survival at the first (HR, 1.34) and second timepoints (HR, 1.14).
• This association between PPI use and worse survival outcomes held regardless of MGMT promoter methylation status.
• Regarding the association between the use of PPIs and steroids, interaction tests were not significant, implying that steroids did not significantly modify the association between the use of PA-PPIs and survival, but a nonsignificant trend suggested greater harm among steroid users.
• No significant association with survival outcomes was observed for other antacid medications after adjusting for prognostic factors.

IN PRACTICE:

The findings of this study suggest that “PA-PPI use should be discouraged in patients with glioblastoma, since alternative agents are available and a detrimental effect cannot be excluded,” the authors of the study concluded.

SOURCE:

The study, led by Emilie Le Rhun, MD, PhD, University Hospital and University of Zurich, Zurich, Switzerland, was published online in JAMA Network Open.

LIMITATIONS:

The study was retrospective, although data were captured prospectively. Drug use was only tracked while patients remained in the trial, potentially affecting overall survival analyses through post-progression pharmacotherapy. Confounding by indication was possible because patients with more severe edema or symptoms were more likely to receive steroids and PPIs. Overall steroid dose, duration of treatment, and timing relative to treatment phases were not captured.

DISCLOSURES:

The study was supported by the European Organisation for Research and Treatment of Cancer Brain Tumor Group. Le Rhun disclosed receiving grants from Bristol Myers Squibb and Servier and personal fees from Bayer, Biodexa/Sitoxi, Janssen, LEO Pharma, medac, My Tomorrows, Pierre Fabre, Roche, Seattle Genetics, and Servier, outside the submitted work. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.