Epidermal growth factor receptor (EGFR) exon 20 mutations in non-small-cell lung cancer and resistance to EGFR-tyrosine kinase inhibitors

Invest New Drugs. 2014 Dec;32(6):1311-5. doi: 10.1007/s10637-014-0146-x. Epub 2014 Aug 23.

Abstract

Introduction: In patients with non-small cell lung cancer (NSCLC), the predictive value of rare epidermal growth factor receptor (EGFR) exon 20 mutations in determining a patient's response to EGFR tyrosine kinase inhibitor (TKI) treatment is unclear.

Patients and methods: We reviewed data for NSCLC patients harboring EGFR exon 20 mutations from two hospitals in Korea. EGFR mutations were analyzed using directional sequencing.

Results: We identified eight patients carrying EGFR exon 20 mutations, seven of whom had insertional mutations. Three patients carried previously unreported insertional mutations. Among six patients who were treated with EGFR TKI, one showed stable disease and three showed primary resistance. Response evaluations were not performed for the other two patients because of their clinical deterioration.

Conclusions: EGFR exon 20 insertional mutations, including three that were previously unreported, were associated with the poor response of patients to TKI treatment.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics*
  • Erlotinib Hydrochloride
  • Exons
  • Female
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib