The effects of switching EGFR‐TKI treatments for non‐small cell lung cancer because of adverse events

Abstract

Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) are used to treat patients with non‐small cell lung cancer (NSCLC) and EGFR driver mutations. Although some patients discontinued these treatments because of adverse events, it is unclear whether switching EGFR‐TKI because of adverse events provides a benefit. Methods This retrospective study evaluated data from 22 patients with EGFR mutation‐positive NSCLC who received at least two EGFR‐TKIs that were switched because of adverse events (March 2011 to September 2017). Progression‐free survival 2 (PFS2) was defined as the time from starting of the first EGFR‐TKI treatment to disease progression during the second EGFR‐TKI treatment. Results Seventeen patients received gefitinib as the first EGFR‐TKI treatment, while four patients received afatinib and one patient received erlotinib. The median time to failure of the first EGFR‐TKI treatment was 1.6 months. The EGFR‐TKIs were switched because of hepatotoxicity (n = 16), interstitial lung disease (n = 3), and other reasons (n = 3). The median washout period was 1.1 months. Seventeen patients received erlotinib as the second EGFR‐TKI treatment, while three patients received gefitinib and two patients received afatinib. The median PFS for the second EGFR‐TKI treatment was 15.2 months. The median PFS2 was 17.7 months and the median overall survival was 32.8 months. Conclusions Switching EGFR‐TKIs because of adverse events provided a clinical benefit for patients with EGFR mutation‐positive NSCLC. Appropriate judgment regarding switching from one EGFR‐TKI to another may improve the performance status and prognosis of patients with EGFR mutation‐positive NSCLC.

Comparison of Different Tyrosine Kinase Inhibitors for Treatment of Poor Performance Status Patients with EGFR-Mutated Lung Adenocarcinoma

“…In contrast, among patients who experienced drug discontinuation, a similar trend of no differences among EGFR-TKIs was found for PFS but not for OS, which might be influenced by the sequential treatment with other EGFR-TKIs [29,30]. These findings should be carefully interpreted, as a limited proportion of patients experienced either dose adjustment or drug discontinuation in the current cohort, except in the 40 mg afatinib group due to the higher level of AEs compared with other EGFR-TKIs [24].…”

FOXO3 mutation predicting gefitinib-induced hepatotoxicity in NSCLC patients through regulation of autophagy

“…Indeed, hepatotoxicity was the main reason of drug switching in EGFR–TKI treatments 44 . In previous clinical case reports, several case studies suggested that erlotinib was a well-tolerated and effective alternative treatment option for patients suffered from gefitinib-induced hepatotoxicity 3 , 25 , implied that the mechanisms of hepatotoxicity induced by gefitinib/erlotinib might be different.…”

Image-guided drug delivery of nanotheranostics for targeted lung cancer therapy

“…Advances in targeted therapy of malignant lung tumors have been led by the development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) which are widely applied in the clinic as the standard first-line option for treating EGFR-mutant NSCLC with category 1 recommendations 8 . Gefitinib (Gef) induces apoptosis by targeting the ATP cleft to prevent EGFR autophosphorylation 9 and has a high clinical benefit 10 .…”