Gastric Acid Suppression Is Associated With Decreased Erlotinib Efficacy in Non-Small-Cell Lung Cancer

Tyrosine kinase inhibitors (TKIs) are the focus in oncology research. As oral drugs, TKIs often have pH-dependent solubility-suggesting interactions with gastric acid suppressants (ASs). This retrospective review of 507 advanced non-small-cell lung cancer (NSCLC) patients treated with erlotinib demonstrates negative outcomes in patients concurrently receiving AS therapy; a finding also seen with sunitinib. Caution is required in this underappreciated interaction. Background: Erlotinib is a key therapy for advanced NSCLC. Concurrent AS therapy with TKIs might reduce TKI plasma levels. Because of gastroesophageal reflux disease prevalence, this retrospective analysis was undertaken to determine if coadministering erlotinib with AS therapy affected NSCLC outcomes. Patients and Methods: Records of advanced NSCLC patients who received erlotinib from 2007 to 2012 at a large, centralized, cancer institution were retrospectively reviewed. Pertinent demographic data were collected and concomitant AS treatment was defined as AS prescription dates overlapping with >= 20% of erlotinib treatment duration. Records of patients who received erlotinib for >= 1 week were analyzed for progression-free survival (PFS) and overall survival (OS). Results: Stage IIIB/IV NSCLC patients (n = 544) were identified and 507 had adequate data for review. The median age was 64 years and 272 were female. Adenocarcinoma (n = 318; 64%) and squamous (n = 106; 21%) were predominant subtypes; 124 patients received concomitant AS therapy. In this unselected population, median PFS and OS in AS versus no AS groups were 1.4 versus 2.3 months (P < .001) and 12.9 versus 16.8 months (P = .003), respectively. Factoring sex, subtype, and performance status in multivariate Cox proportional hazards ratios for PFS and OS between AS and no AS groups were 1.83 (95% confidence interval [CI], 1.48-2.25) and 1.37 (95% CI, 1.11-1.69), respectively. Conclusion: This large population-based study suggests erlotinib efficacy might be linked with gastric pH and OS could be adversely affected. To our knowledge, this is the first study demonstrating a possible negative clinical effect of coadministration of erlotinib with AS therapy. Further prospective investigation is warranted.