Clinical impact of gastric acid suppressing medication on the effectiveness of tyrosine kinase inhibitors in lung cancer patients

Purpose: Erlotinib and gefitinib are both tyrosine kinase inhibitors (TKIs) approved for the treatment of non-small cell lung cancer (NSCLC). Although it is well known that the increase of gastric pH may decrease the solubility of TKIs, there is limited evidence about the clinical repercussion of this fact. The purpose of this study was to determine if the use of gastric acid suppressive therapy (As) concomitantly with TKIs has an adverse impact on progression-free survival (PFS) and to determine whether the type of drug used (proton pump inhibitors/PPIs or histamine-2 receptors antagonists (H2RAs) may influence it. Methods: In this retrospective observational study included were patients treated for ≥1 week with erlotinib or gefitinib from January 2012 to December 2015. Demographic, diagnostic and therapeutic variables were collected. Patients were divided into two groups (As users and non-As users). For the calculation of the PFS the Kaplan Meier and multivariate Cox regression analysis were used. Results: 163 patients with mean age 70 years were included. 72.39% (n=118) received TKIs and As concomitantly. The mean PFS was 84 days (95%CI, 65-101) and 221 days (95%CI, 125-429; p <0.0001) in As users and non-As users, respectively. Regarding the type of As used, no significant differences were observed. Conclusion: Concomitant use of As and TKIs adversely impacted the PFS outcomes in NSCLC patients regardless of the type of As used. Further studies are needed to determine the clinical impact of interactions between antiacids and antineoplastics.