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

Thorac Cancer. 2023 Feb;14(4):348-356. doi: 10.1111/1759-7714.14674. Epub 2022 Dec 16.

Abstract

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.

Keywords: EGFR mutation; EGFR-TKIs; intolerable adverse events; lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Disease-Free Survival
  • ErbB Receptors
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Mutation
  • Protein Kinase Inhibitors / adverse effects
  • Retrospective Studies

Substances

  • Protein Kinase Inhibitors
  • ErbB Receptors
  • EGFR protein, human