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Updated: Jun 2, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Non-Small Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Inhibitors: The Effect of Concurrent
Otto Manninen, Sanna Iivanainen1, Martti Arffman1
1Cancer Center and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
Introduction:
EGFR-tyrosine kinase inhibitor (TKI)-induced rash can be alleviated with tetracyclines (TCN) and topical corticosteroids (TCS), whereas drugs for acid-related disorders (DARDs) can affect EGFR-TKI absorption. The present study investigated the concomitant use of TCNs, TCSs, and DARDs with EGFR-TKIs in non-small cell lung cancer (NSCLC) and whether these affect patient outcomes.
Methods:
We retrospectively collected data from all patients (n = 1,498) who had purchased for EGFR-TKIs (erlotinib, gefitinib, and afatinib) in Finland between 2011 and 2020. Overall survival (OS) and time-on-treatment (ToT) were analyzed from the first EGFR-TKI purchase.
Results:
Early TCN purchases were registered in 298 (19.6%) patients; early TCS and DARD purchases were observed in 154 (10.1%) and 192 (12.9%), while similar percentages were detected in the EGFR mutant cohort. In the entire cohort, early purchase of TCSs and TCNs was associated with improved ToT, OS, and DARDs with inferior outcomes. In the multivariate analysis, TCSs retained their significance in ToT (HR: 0.78; 95% CI: 0.66-0.94), TCNs in OS (HR: 0.73; 95% CI: 0.63-0.84), and DARDs in both (HR: 1.28; 95% CI: 1.091-1.495; HR: 1.19; 95% CI: 1.01-1.41). In the EGFR mutant cohort, similar nonsignificant trends were observed for TCNs, TCSs and DARDs. In the analysis according to EGFR-TKI, erlotinib users had improved outcomes when early TCN or TCS purchases were registered, whereas DARDs were associated with worse outcomes among gefitinib users.
Conclusions:
Among EGFR-TKI-treated NSCLCs, the use of TCN, TCS, and DARD can affect treatment outcomes that should be considered in optimal patient care.
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