Overview of current systemic management of EGFR-mutant NSCLC

Ann Oncol. 2018 Jan 1;29(suppl_1):i3-i9. doi: 10.1093/annonc/mdx702.


Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy is the standard of care for lung cancer patients with sensitising EGFR mutations (exon 19 deletion or L858R mutation). Several phase III studies have demonstrated the superiority of gefitinib, erlotinib (first generation of TKIs) or afatinib (second generation) to chemotherapy in progression-free survival and response rates. Drug-related toxicities, such as diarrhoea, acneiform skin rash, mucositis, and paronychia, are frequently encountered in patients who receive EGFR TKIs. Other rare side-effects, such as hepatic impairment and interstitial lung disease, should be identified early and managed carefully. Patients with uncommon EGFR mutations, such as G719X, S768I, and L861Q, may require special selection of EGFR TKIs. The combination of erlotinib plus bevacizumab has been accepted in certain parts of the world as an alternative front-line treatment. This review article summarizes the studies leading to the establishment of EGFR TKIs in EGFR-mutant lung cancer patients. The side-effect profiles of the current EGFR TKIs in these large trials are listed, and the management of uncommon EGFR mutations is discussed. Finally, the potential role of combination front-line treatment is discussed.

Publication types

  • Review

MeSH terms

  • Acneiform Eruptions / chemically induced
  • Acneiform Eruptions / epidemiology
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / administration & dosage
  • Bevacizumab / adverse effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / etiology
  • Diarrhea / chemically induced
  • Diarrhea / epidemiology
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride / administration & dosage
  • Erlotinib Hydrochloride / adverse effects
  • Exons / genetics
  • Humans
  • Lung Diseases, Interstitial / chemically induced
  • Lung Diseases, Interstitial / epidemiology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods
  • Mucositis / chemically induced
  • Mucositis / epidemiology
  • Paronychia / chemically induced
  • Paronychia / epidemiology
  • Patient Selection
  • Progression-Free Survival
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Randomized Controlled Trials as Topic


  • Protein Kinase Inhibitors
  • Bevacizumab
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors