The influence of gastric secretion inhibitors on gefitinib therapy in patients with non-small cell lung cancer harboring epidermal growth factor receptor activating mutations.

Abstract

e18059 Background: Gefitinib is orally available, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used in patients with non-small cell lung cancer (NSCLC), especially harboring EGFR activating mutations. Pharmacokinetic study revealed absorption of gefitinib was affected by the gastric pH. However, cancer patients in advanced stage are frequently administered gastric secretion inhibitors, such as proton pump inhibitors (PPIs) and H2 blockers (H2Bs) for various reasons. We hypothesized that gastric secretion inhibitors might suppress the efficacy of gefitinib therapy in NSCLC patients with EGFR activating mutations. The purpose of this study is to investigate the influence of PPIs/H2Bs on the efficacy of gefitinib therapy in the patients with NSCLC harboring EGFR activating mutations. Methods: From Apr 2004 to Aug 2011, we retrospectively analyzed the correlation between administration of PPIs/H2Bs and efficacy of gefitinib therapy in the patients with NSCLC harboring EGFR mutations. Results: Forty-three patients with EGFR mutations received gefitinib therapy in our hospital. 65.1% (28/43) patients administered PPIs/H2Bs simultaneously. Patients who received PPIs/H2Bs (PPIs/H2Bs group) had similar response rate compared with patients who didn’t receive PPIs/H2Bs (non-PPIs/H2Bs group) (77.8% vs 73.3%, p=1.00). Median progression free survival was 291 days in PPIs/H2Bs group and 353 days in non-PPIs/H2Bs group ( HR 1.23, Log-rank trest, p=0.578), respectively. Median overall survival was 718 days in PPIs/H2Bs group and not reached in non-PPIs/H2Bs group ( HR 1.53, Log-rank trest, p=0.403), respectively. Conclusions: Gastric secretion inhibitors didn’t affect the efficacy of gefitinib treatment in patients with NSCLC harboring EGFR activating mutations.