The survival after discontinuation of EGFR‐TKIs due to intolerable adverse events in patients with EGFR‐mutated non–small cell lung cancer

BACKGROUND: Epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) are standard treatments for advanced non–small cell lung cancer (NSCLC) patients harboring the EGFR mutation. Patients experiencing intolerable adverse events (AEs) would discontinue EGFR‐TKIs. This study aimed to evaluate the impact of intolerable AEs and subsequent treatment on the survival of patients who discontinued EGFR‐TKIs. PATIENTS: The data of advanced NSCLC patients treated with EGFR‐TKIs as frontline treatment at Chang Gung Memorial Hospitals from June 2014 to March 2018 were retrospectively reviewed. RESULTS: A total of 2190 patients were enrolled and treated with frontline EGFR‐TKIs. In August 2021, 114 (5.2%) patients experienced intolerable AEs requiring discontinuation of EGFR‐TKIs. The time median of EGFR‐TKIs discontinuation was 2.56 months. Age >65 years, females, body weight, and body surface area were associated with the occurrence of intolerable AEs for patients treated with afatinib. Patients experiencing skin/paronychia/mucositis and abnormal liver function test had favorable survivals results. Patients who received subsequent EGFR‐TKIs treatment, experienced better progression‐free survival (PFS), total PFS (from frontline line EGFR‐TKIs), and overall survival (OS) compared to patients receiving chemotherapy or no treatment. Patients undergoing subsequent EGFR‐TKIs had better total PFS (median, 14.9 vs. 11.3 months, p = 0.013) and OS (median, 31.3 vs. 20.1 months, p = 0.001) than patients who did not discontinue because of AEs. Favorable OS was validated by propensity score matching. CONCLUSION: Patients experiencing intolerable AEs during EGFR‐TKI treatment should consider switching to an alternative EGFR‐TKI, which increase the survival results as compared to those patients who did not experience intolerable AEs.