title: Distinct Benefit of Overall Survival between Patients with Non-Small-Cell Lung Cancer Harboring EGFR Exon 19 Deletion and Exon 21 L858R Substitution.
abstract: BACKGROUND
  Exon 19 deletion (Del19) and exon 21 L858R substitution (L858R), which account for 90% of epidermal growth factor receptor (EGFR) mutations as common mutations, are associated with favorable outcomes with EGFR-tyrosine kinase inhibitors (TKIs) compared with other uncommon EGFR mutations in non-small-cell lung cancer (NSCLC). However, whether there are differences in overall survival (OS) between patients with these common EGFR mutations remains controversial.
  
  
  METHODS
  The subjects studied were 74 NSCLC patients with common EGFR mutations treated with gefitinib or erlotinib. Using univariate and multivariate analyses, we retrospectively compared the clinicopahological characteristics of patients harboring Del19 with those harboring L858R.
  
  
  RESULTS
  Compared with patients harboring L858R, EGFR-TKIs provided a significant OS benefit in patients harboring Del19 (p = 0.024), as well as favorable therapeutic responses (p = 0.045) and progression-free survival (PFS) benefits (p = 0.031). In multivariate analyses, Del19 was independently associated with PFS (p = 0.029) and OS (p = 0.009), whereas no parameters other than pleural dissemination at the initial treatment were associated with EGFR mutation types.
  
  
  CONCLUSIONS
  Del19 and L858R have distinct prognostic implications and may require individual therapeutic strategies.
authors.affiliation: Department of Clinical Oncology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Koyama
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yuki
authors.initials: Y
authors.lastname: Iwai
authors.forename: Rumi
authors.initials: R
authors.lastname: Kawamura
authors.forename: Chihiro
authors.initials: C
authors.lastname: Miwa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nagai
authors.forename: Koichi
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Koyama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use; D005091:Exons; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies; D017384:Sequence Deletion
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib