title: Clinical implications of T790M mutation in patients with acquired resistance to EGFR tyrosine kinase inhibitors.
abstract: OBJECTIVE
  Although T790M mutation is considered to be the major mechanism of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC), its clinical implication remains undetermined.
  
  
  METHODS
  Post-progression tumor specimens were prospectively collected for T790M mutation analysis in NSCLC patients with acquired resistance to initial EGFR TKIs. Clinical features were compared between patients with and without T790M.
  
  
  RESULTS
  Out of 70 cases, 36 (51%) were identified to have T790M mutation in the rebiopsy specimen. There was no difference in the pattern of disease progression, progression-free survival for initial TKIs (12.8 and 11.3 months), post-progression survival (14.7 and 14.1 months), or overall survival (43.5 and 36.8 months) in patients with and without T790M. In total, 34 patients received afatinib after post-progression biopsy as a subsequent treatment, and the response rate was 18%. The median progression-free survival for afatinib was 3.7 months for the entire group, and 3.2 and 4.6 months for the groups with and without T790M, respectively (P = 0.33).
  
  
  CONCLUSIONS
  The identification of T790M as acquired resistance mechanism was clinically feasible. Although T790M had no prognostic or predictive role in the present study, further research is necessary to identify patients with T790M-mutant tumors who might benefit from newly developed T790M-specific TKIs.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jong-Mu
authors.initials: JM
authors.lastname: Sun
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003062:Codon; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D009154:Mutation / Q000187:drug effects; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003062:Codon; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: Afatinib; Epidermal growth factor receptor; Resistance; T790M; Tyrosine kinase inhibitor