CLINICAL IMPACTS OF GASTRIC ACID SUPPRESSION THERAPY ON PATIENT WITH ADENOCARCINOMA OF LUNG TREATED WITH GEFITINIB

PURPOSE: Gefitinib was approved by the US Food and Drug Administration (FDA) for treatment of advanced non-small cell carcinoma harboring epidermal growth factor receptor (EGFR) mutations including exon 19 deletion or the exon 21 (L858R) substitution mutation since 2003. Gastric acid suppressing agents is known to inhibit gefitinib absorption and reduces its plasma concentration, but retrospective studies on its effect on actual patient’s progression free survival have yielded variable results, possibly due to the heterogeneity in study cohort and the study design. METHODS: This is a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong that included 193 Chinese patients with advanced adenocarcinoma of lung who had common sensitizing EGFR mutation and received gefitinib as first-line treatment. Patients who took gastric acid suppressing agents, namely histamine-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI) was compared with those who did not. The primary end-point is progression-free survival (PFS) and the differences in side effect profile. RESULTS: Patients taking gastric acid suppressants have significantly worse PFS, especially for those on proton pump inhibitor (median 368 vs 189 vs 166 days - For non-acid suppressant group, H2RA group and PPI group, respectively). Hazard ratio were 2.273 (95% CI 1.541 – 3.352) for H2RA group and 3.385 for PPI group (95% CI 2.181 – 5.255) respectively (p value <0.001). CONCLUSIONS: Co-administration of gastric acid suppressants with gefitinib is associated with worse progression-free survival. CLINICAL IMPLICATIONS: Co-administration of gastric acid suppressant significantly reduce the PFS in patient with advanced stage adenocarcinoma of lung on first line Gefitinib.