title: Clinical outcomes in non-small cell lung cancers harboring different exon 19 deletions in EGFR.
abstract: OBJECTIVE
  Several deletions in exon 19 of epidermal growth factor receptor (EGFR) gene have been reported in non-small cell lung cancer (NSCLC). It is unknown if deletions occurring at different amino acid positions or of different sizes are associated with different clinical outcome to EGFR tyrosine kinase inhibitors (TKI).
  
  
  METHODS
  This study enrolled NSCLC patients with deletions in EGFR exon 19. Patients who had received EGFR TKIs for advanced NSCLC were further evaluated for response rate (RR), progression-free survival (PFS), and overall survival (OS).
  
  
  RESULTS
  In 308 patients with deletions in EGFR exon 19, 298 had deletions encompassing the entire amino acid string from L747 through E749 (LRE deletions). EGFR TKIs were used in 204 patients with advanced NSCLC. Patients with non-LRE deletions had the least RR, compared with those with deletions from E746 or L747 (42.9%, 68.2%, and 79.6%, respectively; P = 0.022). Patients with non-LRE deletions had relatively short median PFS, though not significantly different from those with deletions from E746 or L747 (5.9, 9.8, and 10.5 months, respectively; P = 0.665). The OS was not different among patients with deletions occurring at different amino acid positions (P = 0.776). Deletions in exon 19 of different sizes were not associated with different RR, PFS, or OS.
  
  
  CONCLUSIONS
  Non-LRE deletions in exon 19 were associated with worse response to EGFR TKIs, compared with LRE deletions. Therefore, the expected clinical outcome under EGFR TKIs depends on not only the existence but also the types of deletions in exon 19.
authors.affiliation: Department of Laboratory Medicine, Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Kuei-Pin
authors.initials: KP
authors.lastname: Chung
authors.forename: Shang-Gin
authors.initials: SG
authors.lastname: Wu
authors.forename: Jenn-Yu
authors.initials: JY
authors.lastname: Wu
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.forename: Pin-Fei
authors.initials: PF
authors.lastname: Wei
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Shih
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D020539:Sequence Analysis, Protein; D017384:Sequence Deletion; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors