Effectiveness of Treatments for Advanced Non-Small-Cell Lung Cancer With Exon 20 Insertion Epidermal Growth Factor Receptor Mutations

Clin Lung Cancer. 2019 Nov;20(6):e620-e630. doi: 10.1016/j.cllc.2019.06.018. Epub 2019 Jun 26.


Background: Two main categories of epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) patients are deletions in exon 19 and L858R in exon 21. Treatments of advanced NSCLC patients with these mutations are well documented, and clinical responses to tyrosine kinase inhibitors (TKIs) are favorable. However, effective treatments for patients with exon 20 insertion mutations are not well verified. We investigated the clinical response to various treatments (chemotherapy and TKIs) of advanced NSCLC patients with EGFR exon 20 insertions.

Patients and methods: In this study, specimens from 3805 NSCLC patients were examined for EGFR mutations. Different first-line treatments and their effectiveness in NSCLC patients with exon 20 insertion EGFR mutations were investigated.

Results: In the cohort of the 3805 patients, 2112 (55.5%) had EGFR mutations, including 84 patients (4.0%) with exon 20 insertion mutations. Efficacy of different first-line chemotherapy or TKIs were evaluated. Pemetrexed-containing therapies were related to better progression-free survival (6.2 vs. 2.7 months; P < .001) and overall survival (28.0 vs. 15.4 months; P = .009) than regimens without pemetrexed. Patients with exon 20 insertions had a poor response to TKIs. However, the mutation Ala763_Tyr764insPheGlnGluAla (A763_Y764 insFQEA) was related to a favorable response to TKIs.

Conclusion: Exon 20 insertion EGFR mutations comprised a considerable group of the entire population of patients with EGFR mutations. Different first-line treatments and variants of the exon 20 insertions might be related to different outcomes in advanced NSCLC patients.

Keywords: Epidermal growth factor receptor; Exon 20; Lung cancer; Mutations; Pemetrexed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Cohort Studies
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Exons / genetics*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutagenesis, Insertional / genetics*
  • Neoplasm Staging
  • Protein Kinase Inhibitors / therapeutic use*
  • Survival Analysis
  • Treatment Outcome


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