EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: a retrospective database analysis of potential drug interaction
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Nesaretnam Barr Kumarakulasinghe1,*, Nicholas Syn1,2,3,*, Yu Yang Soon4, Atasha Asmat5, Huili Zheng6, En Yun Loy6, Brendan Pang2,7, Ross Andrew Soo1,2
1Department of Haematology-Oncology, National University Cancer Institute, Singapore
2Cancer Science Institute of Singapore, National University of Singapore, Singapore
3Yong Loo Lin School of Medicine, National University of Singapore, Singapore
4Department of Radiation Oncology, National University Cancer Institute, Singapore
5Department of General Surgery, Tan Tock Seng Hospital, Singapore
6National Registry of Diseases Office, Health Promotion Board, Singapore
7Department of Pathology, National University Health System, Singapore
*These authors have contributed equally to this work as co-first authors
Ross Andrew Soo, email: [email protected]
Keywords: gefitinib, erlotinib, drug-drug interactions, NSCLC, gastric acid suppression
Received: August 19, 2016 Accepted: October 27, 2016 Published: November 19, 2016
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.
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