title: EGFR mutations predict survival benefit from gefitinib in patients with advanced lung adenocarcinoma: a historical comparison of patients treated before and after gefitinib approval in Japan.
abstract: OBJECTIVE
  This study evaluated whether the presence of epidermal growth factor receptor (EGFR) mutations is a predictive marker for survival benefit from gefitinib and/or a prognostic marker in patients with advanced lung adenocarcinoma.
  
  
  METHODS
  Overall survival (OS) was compared between patients with advanced lung adenocarcinoma who began first-line systemic therapy before and after gefitinib approval in Japan (January 1999 to July 2001 and July 2002 to December 2004, respectively). Deletional mutations in exon 19 or the L858R mutation in exon 21 of EGFR were evaluated using high-resolution melting analysis.
  
  
  RESULTS
  EGFR mutations were detected in 136 (41%) of the 330 patients included in this study. OS was significantly longer among the EGFR-mutant patients treated after gefitinib approval compared with the OS of patients treated before gefitinib approval (median survival time [MST], 27.2 v 13.6 months, respectively; P < .001), whereas no significant survival improvement was observed in patients without EGFR mutations (MST, 13.2 v 10.4 months, respectively; P = .13). A significant interaction between the presence of EGFR mutations and a survival improvement was seen (P = .045). Among patients treated before gefitinib approval, those with EGFR mutations lived longer than those without EGFR mutations (MST, 13.6 v 10.4 months, respectively; P = .034). The response rates to first-line cytotoxic chemotherapy were not significantly different between patients with and without EGFR mutations (31% v 28%, respectively; P = .50).
  
  
  CONCLUSIONS
  EGFR mutations significantly predict both a survival benefit from gefitinib and a favorable prognosis in patients with advanced lung adenocarcinoma.
authors.affiliation: Division of Internal Medicine, Research Center for Cancer Prevention and Screening, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Takano
authors.forename: Tomoya
authors.initials: T
authors.lastname: Fukui
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sekine
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Koh
authors.initials: K
authors.lastname: Furuta
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib