Combination Use of First-Line Afatinib and Proton-Pump Inhibitors Reduces Overall Survival Among Patients with EGFFR Mutant Lung Cancer

Meng-Chin Ho; Ying-Shan Chung; Yu-Ching Lin; Ming-Szu Hung; Yu-Hung Fang

doi:10.2147/OTT.S387165

Combination Use of First-Line Afatinib and Proton-Pump Inhibitors Reduces Overall Survival Among Patients with EGFFR Mutant Lung Cancer

Onco Targets Ther. 2022 Dec 28:15:1573-1582. doi: 10.2147/OTT.S387165. eCollection 2022.

Authors

Meng-Chin Ho¹, Ying-Shan Chung^{2

3}, Yu-Ching Lin^{1

4}, Ming-Szu Hung^{1

4

5}, Yu-Hung Fang^{1

3}

Affiliations

¹ Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Puzi City, Chiayi County, Taiwan, Republic of China.
² Department of Pharmacy, Chang Gung Memorial Hospital, Puzi City, Chiayi County, Taiwan, Republic of China.
³ Department of Nursing, Chang Gung University of Science and Technology, Puzi City, Chiayi County, Taiwan, Republic of China.
⁴ Department of Respiratory Care, Chang Gung University of Science and Technology, Puzi City, Chiayi County, Taiwan, Republic of China.
⁵ School of Medicine, College of Medicine, Chang Gung University, Guishan Township, Taoyuan County, Taiwan, Republic of China.

Abstract

Purpose: Previous retrospective studies reported that proton-pump inhibitors (PPIs) may decrease the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) including gefitinib and erlotinib. Afatinib had a wider soluble pH range, with possible fewer interactions with antacids. However, clinical data were limited. Thus, this study aimed to evaluate the negative impact of PPIs on afatinib.

Patients and methods: This retrospective cohort study included patients who are newly diagnosed with non-small cell lung cancer (NSCLC) from 2014 to 2019 using the Chang Gung Research Database. We identified patients who were treated with first-line afatinib and analyzed the association between the PPI and afatinib treatment outcomes.

Results: A total of 1418 patients were treated with first-line afatinib and followed up for 6 years. First-line afatinib was administered to 918 eligible patients, and 330 had afatinib with PPIs. The combination use of PPIs and afatinib significantly decreased the overall survival (OS) compared with that of patients using afatinib only (median OS: 33.2 and 25.1 months, p < 0.01) and multivariate analyses (Combination use: hazard ratio: 1.29; 1.05-1.59, p = 0.01). The percentages of patients who were able to receive 2nd line therapy also significantly decreased in afatinib with PPI cohort.

Conclusion: The concurrent use of PPIs was associated with lower OS in patients with EGFR-mutant lung cancer under the first-line afatinib treatment but not associated with TTF.

Keywords: Chang Gung Research Database; afatinib; epidermal growth factor receptor tyrosine kinase inhibitor; non-small cell lung cancer; proton-pump inhibitor.

Grants and funding

This study was supported by a grant from Chang Gung Memorial Hospital, Chia-Yi branch, Taiwan (CGRPG6K0041). This funding body played no role in the study design, analysis, and interpretation of data in this paper.