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

(E-pub Ahead of Print)

Author(s): Wang Chun Kwok, James Chung Man Ho, David Chi Leung Lam, Macy Mei Sze Lui, Mary Sau Man Ip, Terence Chi Chun Tam*.

Journal Name: Clinical Cancer Drugs

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Background: Gefitinib was approved by the Food and Drug Administration (FDA) of the United States (US) for treatment of advanced non-small cell carcinoma harboring sensitizing epidermal growth factor receptor (EGFR) mutations. Gastric acid suppressing medication use inhibits gefitinib absorption and reduces its plasma concentration but retrospective studies on whether there is 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 gastric acid suppressing medication use 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. that included 193 Chinese patients with advanced adenocarcinoma of lung harboring common sensitizing EGFR mutations who received gefitinib as 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), was compared with those who did not (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 have 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).

Conclusions: Co-administration of gastric acid suppressants with gefitinib is associated with shorter progression-free survival and overall survival.

Keywords: Lung cancer, gefitinib, proton pump inhibitor, epidermal growth factor receptor, gastric acid suppression, tyrosine kinase inhibitor

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(E-pub Ahead of Print)
DOI: 10.2174/2212697X06666191021155535