Uncommon EGFR mutations in advanced non-small cell lung cancer

Lung Cancer. 2017 Jul;109:137-144. doi: 10.1016/j.lungcan.2017.04.016. Epub 2017 Apr 27.

Abstract

Molecular profiling in advanced non-small cell lung cancer (NSCLC) has allowed for the detection of actionable mutations, which has revolutionized the treatment paradigm in this highly fatal disease. Mutations involving the epidermal growth factor receptor (EGFR) gene are most common and the 'classical mutations', exon 19 deletions and the point mutation L858R at exon 21, predict response to EGFR tyrosine kinase inhibitors (TKIs). The 'uncommon' EGFR mutations account for 10-18% of all EGFR mutations and primarily consist of exon 20 insertions, exon 18 point mutations and complex mutations. Improved detection techniques have broadened the spectrum of reported aberrations within the 'uncommon group' but response to TKIs is variable and not fully elucidated. This review provides an overview of the biology and incidence of uncommon EGFR mutations and summarizes reported outcomes when treated with EGFR-TKIs.

Keywords: EGFR mutations; NSCLC; Tyrosine kinase inhibitors; Uncommon.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Drug Resistance
  • ErbB Receptors / genetics*
  • Humans
  • Incidence
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Mutation / genetics*
  • Protein Kinase Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

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