JAMA network open · 2025
Proton Pump Inhibitor Use and Survival in Patients With Newly Diagnosed Glioblastoma.
СтатьяМетаанализПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Le Rhun Emilie, Sain Debaleena, Erridge Sara C, Reardon David A, Minniti Giuseppe, Roth Patrick, Wick Wolfgang, Nabors Burt, Sampson John, Mason Warren, Cloughesy Tim, Reijneveld Jacob C, Stupp Roger, Preusser Matthias, Gorlia Thierry, Weller Michael
Аннотация
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 of resection, and MGMT status confirmed a difference for PFS at landmarks 1 (hazard ratio [HR], 1.14 [95% CI, 1.01-1.28]), 2 (HR, 1.26 [95% CI, 1.09-1.44]), and 3 (HR, 1.31 [95% CI, 1.10-1.56]), and for OS at landmarks 1 (HR, 1.34 [95% CI, 1.08-1.66]) and 2 (HR, 1.14 [95% CI, 1.01-1.29]). No such association was seen for the use of other antacid drugs. The negative association of PA-PPI use with PFS and OS was observed independently of MGMT promoter methylation and steroid use.
CONCLUSIONS AND RELEVANCE: In this meta-analysis of patients with newly diagnosed glioblastoma, PPI use was associated with inferior survival outcomes. These findings suggest that PA-PPI use should be discouraged in patients with glioblastoma, since alternative agents are available and a detrimental effect cannot be excluded. Translational research studies should explore whether PPI-induced activity of ALDH mediates the potential adverse effects of PPI in glioblastoma. .
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 of resection, and MGMT status confirmed a difference for PFS at landmarks 1 (hazard ratio [HR], 1.14 [95% CI, 1.01-1.28]), 2 (HR, 1.26 [95% CI, 1.09-1.44]), and 3 (HR, 1.31 [95% CI, 1.10-1.56]), and for OS at landmarks 1 (HR, 1.34 [95% CI, 1.08-1.66]) and 2 (HR, 1.14 [95% CI, 1.01-1.29]). No such association was seen for the use of other antacid drugs. The negative association of PA-PPI use with PFS and OS was observed independently of MGMT promoter methylation and steroid use.
CONCLUSIONS AND RELEVANCE: In this meta-analysis of patients with newly diagnosed glioblastoma, PPI use was associated with inferior survival outcomes. These findings suggest that PA-PPI use should be discouraged in patients with glioblastoma, since alternative agents are available and a detrimental effect cannot be excluded. Translational research studies should explore whether PPI-induced activity of ALDH mediates the potential adverse effects of PPI in glioblastoma. .