Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Abstract

Background: Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases.

Materials and methods: This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC) who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users.

Results: Fifty-seven patients (57/269, 21.2%) were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234). However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002). Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041). Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases.

Conclusion: Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases.

Fig 1. The inclusion, screening, and group assignments for this study.

Among 1,386 patients who were diagnosed with non-small-cell lung cancer between January 2011 and January 2014, 269 patients were included in the final analysis.

Fig 2. Progression-free survival (PFS) and overall survival (OS) according to antacid use among patients with epidermal growth factor receptor-mutant non-small-cell lung cancer who were treated using first-line tyrosine kinase inhibitors.

(top) PFS among patients who were receiving proton pump inhibitors, histamine H2-receptor antagonists, or no antacid. (bottom) OS among patients who were receiving proton pump inhibitors, histamine H2-receptor antagonists, or no antacid.

Fig 3. The effect of antacids use and metastasis sites on progression-free survival (PFS) and overall survival (OS) among patients with epidermal growth factor receptor-mutant non-small-cell lung cancer who were treated using first-line tyrosine kinase inhibitors.

(A) PFS and (B) OS among patients with brain metastases according to antacid use. (C) PFS and (D) OS among patients with bone metastases according to antacid use. (E) PFS and (F) OS among patients with liver metastases according to antacid use. (G) PFS and (H) OS among patients with pleural metastases according to antacid use.