EGFR-mutated stage IV non-small cell lung cancer: What is the role of radiotherapy combined with TKI?

Cancer Med. 2021 Sep;10(18):6167-6188. doi: 10.1002/cam4.4192. Epub 2021 Aug 10.


Lung cancer is the leading cause of cancer-related death globally and poses a considerable threat to public health. Asia has the highest prevalence of epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC). Despite the reasonable response and prolonged survival associated with EGFR-tyrosine kinase inhibitor (TKI) therapy, the acquisition of resistance to TKIs remains a major challenge. Additionally, patients with EGFR mutations are at a substantially higher risk of brain metastasis compared with those harboring wild-type EGFR. The role of radiotherapy (RT) in EGFR-mutated (EGFRm) stage IV NSCLC requires clarification, especially with the advent of next-generation TKIs, which are more potent and exhibit greater central nervous system activity. In particular, the feasible application of RT, including the timing, site, dose, fraction, and combination with TKI, merits further investigation. This review focuses on these key issues, and provides a flow diagram with proposed treatment options for metastatic EGFRm NSCLC, aiming to provide guidance for clinical practice.

Keywords: EGFR mutation; TKI; radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / prevention & control*
  • Brain Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chemoradiotherapy / methods*
  • Drug Resistance, Neoplasm / radiation effects
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Mutation
  • Neoplasm Staging
  • Progression-Free Survival
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*


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