title: Clinical predictors versus epidermal growth factor receptor mutation in gefitinib-treated non-small-cell lung cancer patients.
abstract: BACKGROUND
  Clinical predictors including Asian, female, adenocarcinoma and never-smoker and epidermal growth factor mutation are associated with gefitinib responsiveness in non-small-cell lung cancer. Direct comparison between clinical predictors and EGFR mutation for their predictive power has not been reported.
  
  
  METHODS
  For 120 Korean NSCLC patients treated with gefitinib, we have analyzed EGFR mutational status in exons 18, 19 and 21. Patients were grouped according to the number of clinical predictors (female, adenocarcinoma and never-smoker). Response rate (RR), time-to-progression (TTP) and overall survival (OS) were analyzed. Multivariate analysis was performed to investigate which approach yielded better prediction.
  
  
  RESULTS
  RRs according to number of clinical predictors were 0: 3.4%, 1: 17.1%, 2: 29.4% and 3: 33.3% (p=0.002). Patients with gefitinib-sensitive EGFR mutation showed 61.9% RR compared with 12.1% in the remaining patients (p<0.001). RRs were higher in patients with the EGFR mutations regardless of the number of clinical predictors. In multivariate analysis, gefitinib-sensitive EGFR mutation showed higher odds ratio of response (9.6, 95% confidence interval [CI] 3.2-28.7) compared with number of clinical predictors (1.7, 95% CI 1.1-2.7). Hazard ratio (HR) of TTP was also better in gefitinib-sensitive EGFR mutation (0.24, 95% CI 0.12-0.47) than number of clinical predictors (0.83, 95% CI 0.69-0.99). Only gefitinib-sensitive EGFR mutation was associated with improved OS (HR 0.25, 95% CI 0.12-0.52).
  
  
  CONCLUSIONS
  EGFR mutation should be analyzed whenever possible for effective prediction of objective benefit from gefitinib in NSCLC patients with one or more clinical predictors.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Republic of Korea.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Han
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: Kyung-Hun
authors.initials: KH
authors.lastname: Lee
authors.forename: Pil Gyu
authors.initials: PG
authors.lastname: Hwang
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D012727:Sex Characteristics; D012907:Smoking; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib