Concomitant Gastric Acid Suppressants on the Survival of Patients with Non-Small-Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Meta-Analysis

Abstract

Background. The influence of concomitant use of gastric acid suppressants (AS) on survival of patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inconsistent according to previous studies. We performed a meta-analysis to evaluate the effect of additional AS in patients with NSCLC taking TKIs. Methods. Relevant observational studies were identified by a search of Medline, Embase, and Web of Science databases. Only studies with multivariate analyses were included. A random-effect model was used to combine the results. Results. Thirteen retrospective studies with 12259 patients were included. Pooled results showed that concomitant use of AS was associated with worse progression-free survival (PFS, adjusted hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.31 to 1.89, $P<0.001$ ; I2 = 65%) and overall survival (OS, adjusted HR: 1.38, 95% CI: 1.19 to 1.61, $P<0.001$ ; I2 = 70%) in NSCLC patients taking TKIs. Sensitivity analysis limited to studies including NSCLC with EGFR mutation showed consistent results (HR for PFS: 1.53, $P=0.003$ ; HR for OS: 1.43, $P=0.001$ ). Subgroup analyses indicated that the association between concomitant use of AS and poor survival was not significantly affected by the category of AS used (proton pump inhibitors or histamine type-2 receptor antagonists) or the country of the study (Asian or non-Asian, $P$ for subgroup analysis all >0.05). Conclusions. Concomitant use of AS in patients with NSCLC taking TKIs may be associated with poor survival outcomes.