Clinical Impact of Gastric Acid Suppressants Use on the Efficacy of Gefitinib in Patients with Advanced Adenocarcinoma of the Lung Harboring Common EGFR Mutations

Abstract

Background: Gefitinib was approved by the Food and Drug Administration (FDA) of the United States (US) for the treatment of advanced non-small cell carcinoma harboring sensitizing epidermal growth factor receptor (EGFR) mutations. The use of gastric acid-suppressing medication inhibits gefitinib absorption and reduces its plasma concentration, but retrospective studies on whether there is the corresponding repercussion on progression-free survival (PFS) have yielded variable results, mainly due to heterogeneity in study cohorts and study designs.

Objectives: To assess the clinical impact of the use of gastric acid-suppressing medication in patients on first-line gefitinib for NSLC harboring common EGFR mutation.

Methods: This is a retrospective cohort study conducted in a single, tertiary referral center in Hong Kong S.A.R., which included 193 Chinese patients with advanced adenocarcinoma of lung harboring common sensitizing EGFR mutations who received gefitinib as the first-line treatment. The progression- free survival (PFS) and overall survival (OS) for patients who took gastric acid-suppressing agents, namely histamine-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI), were compared with those who did not take such medication (control group).

Results: Despite the universal practice to separate the medicating time of gastric acid suppressants and EGFR-TKIs by 12 hours, patients who were on gastric acid suppressants had significantly shorter PFS, especially for those on proton pump inhibitor (Median 368 vs. 189 vs. 166 days - For control, H2RA group and PPI group respectively, p-value <0.001). The OS is also significantly shorter for those taking gastric acid suppressants (Median 825 vs. 485 vs. 422 days - For control, H2RA group and PPI group respectively, p-value <0.001).

Conclusion: The co-administration of gastric acid suppressants with gefitinib is associated with shorter progression-free survival and overall survival.