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

BackgroundAntacid 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 MethodsThis 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.ResultsFifty-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.ConclusionAntacid 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.

<p>Concurrent proton-pump inhibitors increase risk of death for lung cancer patients receiving 1st-line gefitinib treatment - a nationwide population-based study</p>

“…Risk of death among patients with low and high PPI coverage ratios was increased 29% and 67%, respectively. This result was essentially compatible with results of previous study by Chen et al18 Similarly, Sharma et. al recently reported that concomitant TKI-PPI treatment adversely affected OS using the SEER-Medicare database 21.…”

“…In healthy volunteers, PPI use may decrease the AUC and peak plasma concentration of first-generation EGFR-TKIs 15. However, the clinical impact of PPIs on the treatment outcome of EGFR-TKIs remains controversial 12,16–18. There have been few large, multi-center studies focused on patients receiving first-line EGFR-TKIs, and all the studies enrolled patients being treated with other antacid agents, not PPIs only.…”

A Survival Scoring System for Non-Small Cell Lung Cancer Patients with De Novo Bone Metastases

“…[26, 35–37] Our study revealed that patients with bone metastases only had better outcomes than those who had distant metastasis at sites other than bone.…”

Impact of Use of Gastric-Acid Suppressants and Oral Anticancer Agents on Survival Outcomes: A Systematic Review and Meta-Analysis

“…A total of 353 potentially eligible records were identified in the electronic databases. After exclusion of n=337 not pertinent papers, n=16 were selected for inclusion in quantitative analysis (n=372,418 patients included, with 12% of patients receiving concomitant GAS therapy) [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] All studies were retrospective except for a pooled analysis of phase 2-3 studies by Lalani et al and a secondary analysis of a randomized prospective trial by Chu et al Oncologic treatment consisted in oral TKIs in n=11 studies, while in n=4 studies patients received oral chemotherapy (i.e. capecitabine); one study did not include information regarding the type of study drugs.…”