EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: a retrospective database analysis of potential drug interaction

Abstract

BackgroundErlotinib and gefitinib are weak base drugs whose absorption and clinical efficacy may be impaired by concomitant gastric acid suppressive (AS) therapy, yet proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2As) are widely indicated in non-small cell lung cancer (NSCLC) patients for the prevention and treatment of erlotinib-induced gastrointestinal injury and corticosteroid-associated gastric irritation. We assessed the clinical relevance of this potential drug-drug interaction (DDI) in a retrospective cohort of EGFR-mutant NSCLC patients.ResultsThe AS usage rate was 35%. In the overall cohort, AS users did not experience poorer OS (HR: 1.47, 95% CI: 0.92 – 2.35, P = 0.10; median, 11.4 versus 17.5 months) or PFS (HR = 1.37, 95% CI: 0.89 – 2.12, P = 0.16; median, 7.6 versus 8.7 months) compared with non-users in multivariate Cox regression analysis. However, subgroup analyses indicated that AS usage was associated with significantly poorer OS and PFS in patients who had fewer or milder comorbidities (Charlson comorbidity index ≤ 2), those with Karnofsky performance status < 90, and never-smokers.Materials and MethodsA retrospective database analysis of 157 patients given erlotinib or gefitinib for EGFR-mutant advanced NSCLC from two institutions was conducted. Patients were classified as AS-users if the periods of AS and anti-EGFR therapy overlapped by ≥ 30%. Overall survival (OS) and progression-free survival (PFS) were assessed according to AS usage.ConclusionsConcomitant AS therapy did not have an adverse impact on OS and/or PFS in the overall cohort. Our subgroup findings should be regarded exploratory and require replication in a large prospective cohort.

The efficacy of first-line tyrosine kinase inhibitors combined with co-medications in Asian patients with EGFR mutation non-small cell lung cancer

“…Of note, in that study 26 , patients were unselected for activating EGFR mutations. Two retrospective cohort studies 11,27 , involving 157 and 130 patients treated with erlotinib or gefitinib, respectively, for the treatment of EGFR mutation-positive advanced NSCLC have been conducted. These studies showed that the combination of EGFR-TKIs with antacid did not affect the efficacy of erlotinib and gefitinib.…”

Effect of Sustained Elevated Gastric pH Levels on Gefitinib Exposure

“…25 In a more recent retrospective database analysis of 157 patients with EGFR mutation-positive NSCLC treated with gefitinib or erlotinib, concomitant gastric acid suppressive therapy was not found to have an adverse impact on overall survival or progression-free survival. 26 Similar results were found in another review of 130 patients with advanced EGFR mutationpositive NSCLC treated with gefitinib or erlotinib (of whom 47 received gastric acid suppressive therapy), with no significant differences found in objective response rate (64% in those who received gastric acid suppressive therapy versus 63% in those who did not; P = .92), median progression-free survival (8.7 versus 10.7 months, respectively; P = .13), or toxicity. 27 Larger long-term studies to investigate further the clinical impact of elevated gastric pH from gastric acid suppressive agents or physiological conditions on the efficacy of gefitinib are warranted.…”

Impact of Use of Gastric-Acid Suppressants and Oral Anticancer Agents on Survival Outcomes: A Systematic Review and Meta-Analysis

“…A total of 353 potentially eligible records were identified in the electronic databases. After exclusion of n=337 not pertinent papers, n=16 were selected for inclusion in quantitative analysis (n=372,418 patients included, with 12% of patients receiving concomitant GAS therapy) [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. The search results and characteristics of the included studies are presented in figure 1 and tables 1-2.…”