Impact of concomitant use of anti-acid agents on efficacy of gefitinib in EGFR-mutant non-small-cell lung cancer (NSCLC).

Abstract

e19008 Background: Gefitinib, an EGFR-tyrosine kinase inhibitor, is an essential agent for EGFR-mutant NSCLC. The preclinical studies revealed its reduced area under the curve (AUC) by elevation of pH in GI tract, potentially leading to alteration in the absorption of gefitinib. It, however, has been controversial as to whether and how simultaneous use of anti-acid agents, commonly used in clinical practices, could alter the sensitivity of gefitinib, especially in EGFR-mutant NSCLC. Thus, we conducted a retrospective cohort study to clarify this issue. Methods: We evaluated progression-free survival (PFS) and overall survival (OS) from the medical charts of chemotherapy-naïve patients with EGFR-mutant NSCLC treated with gefitinib monotherapy in our institution. We also identified history of concomitant use of anti-acid agents (proton pomp inhibitors and histamine type 2 receptor blockers) at the time of initiation of gefitinib therapy and assessed its impact on the efficacy of gefitinib using Cox’s proportional hazard model. Results: Between 2006 and 2012, consecutive 83 patients received gefitinib therapy, of whom 29 (34.9%) used anti-acid agents simultaneously. Baseline clinical characteristics between the two groups (use and non-use of anti-acid agents) were well balanced except performance status (PS) of 0: 17.2% vs. 37.0% respectively. Neither PFS nor OS were influenced by concomitant use of anti-acid agents in univariate analysis (hazard ratio: 1.12; 95% confidence interval: 0.66-1.92 and 1.67; 0.86-3.44, respectively). Multivariate analysis also showed no significant effect of anti-acid agent use on PFS and OS (1.18; 0.67-2.06 and 1.66; 0.81-3.38, respectively), whilst poor PS affected OS (2.03; 1.27-3.26). Additionally, no difference in the impact of use of anti-acid agents on the gefitinib sensitivity was observed when stratified by the type of EGFR mutations. Conclusions: Concomitant use of anti-acid agents does not seem to affect efficacy of gefitinib in EGFR-mutant NSCLC. It is unlikely that physicians need to keep in mind the drug interaction of gefitinib and anti-acid agents in daily clinical practices, although further extensive cohort studies are warranted.