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EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: a retrospective database analysis of potential drug interaction. (Oncotarget, Nov 2016)

Kumarakulasinghe NB, Syn N1,2,3 , Soon YY, Asmat A, Zheng H, Loy EY, Pang B2,7 , Soo RA1,2.

1 Department of Haematology-Oncology, National University Cancer Institute, Singapore.
2 Cancer Science Institute of Singapore, National University of Singapore, Singapore.
3 Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
4 Department of Radiation Oncology, National University Cancer Institute, Singapore.
5 Department of General Surgery, Tan Tock Seng Hospital, Singapore.
6 National Registry of Diseases Office, Health Promotion Board, Singapore.
7 Department of Pathology, National University Health System, Singapore.

Abstract

BACKGROUND:
Erlotinib 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.

RESULTS:
The 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 METHODS:
A 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.

CONCLUSIONS:
Concomitant 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.

KEYWORDS:
NSCLC; drug-drug interactions; erlotinib; gastric acid suppression; gefitinib

PMID: 27907909