The different efficacy of gefitinib or erlotinib according to epidermal growth factor receptor exon 19 and exon 21 mutations in Korean non-small cell lung cancer patients

J Cancer Res Clin Oncol. 2011 Apr;137(4):687-94. doi: 10.1007/s00432-010-0928-2. Epub 2010 Jun 16.

Abstract

Background: Epidermal growth factor receptor (EGFR) mutations are associated with sensitivity to gefitinib or erlotinib in non-small cell lung cancer (NSCLC). We investigated the relationships between the two most common types of somatic EGFR mutations, exon 19 deletions and L858R mutations, and clinical outcomes of Korean NSCLC patients after treatment with gefitinib or erlotinib.

Patients and methods: In Korean patients with NSCLC, EGFR exon 19 deletions and EGFR L858R mutation were identified from tumor specimens obtained before treatment with gefitinib or erlotinib. The response rates, progression-free survival (PFS), and overall survival (OS) were compared between the two groups.

Results: A total of 77 patients with either an exon 19 deletion (n = 58) or L858R mutation (n = 19) were treated with gefitinib or erlotinib. The overall response rate was 69%. Patients with an exon 19 deletion had a significantly longer PFS compared with patients with L858R mutation (9.5 vs. 7.7 months; P = 0.029). The L858R mutation was independently associated with a shorter PFS compared with an exon 19 deletion, even after adjusting for other clinical factors (hazard ratio 2.72; 95% CI 1.38-5.38). However, there were no significant differences in response rate (71 vs. 63%) and OS (21.4 vs. 30.7 months) between subjects with exon 19 deletions and L858R mutations, respectively.

Conclusions: In Korean NSCLC patients, EGFR exon 19 deletions are associated with longer PFS compared with EGFR L858R mutations. These observations need to be confirmed by large-scale studies of patients.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Disease-Free Survival
  • ErbB Receptors / genetics*
  • Erlotinib Hydrochloride
  • Exons*
  • Female
  • Gefitinib
  • Genotype
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation*
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use*
  • Salvage Therapy

Substances

  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Gefitinib