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).