title: Erlotinib in lung cancer - molecular and clinical predictors of outcome.
abstract: BACKGROUND
  A clinical trial that compared erlotinib with a placebo for non-small-cell lung cancer demonstrated a survival benefit for erlotinib. We used tumor-biopsy samples from participants in this trial to investigate whether responsiveness to erlotinib and its impact on survival were associated with expression by the tumor of epidermal growth factor receptor (EGFR) and EGFR gene amplification and mutations.
  
  
  METHODS
  EGFR expression was evaluated immunohistochemically in non-small-cell lung cancer specimens from 325 of 731 patients in the trial; 197 samples were analyzed for EGFR mutations; and 221 samples were analyzed for the number of EGFR genes.
  
  
  RESULTS
  In univariate analyses, survival was longer in the erlotinib group than in the placebo group when EGFR was expressed (hazard ratio for death, 0.68; P=0.02) or there was a high number of copies of EGFR (hazard ratio, 0.44; P=0.008). In multivariate analyses, adenocarcinoma (P=0.01), never having smoked (P<0.001), and expression of EGFR (P=0.03) were associated with an objective response. In multivariate analysis, survival after treatment with erlotinib was not influenced by the status of EGFR expression, the number of EGFR copies, or EGFR mutation.
  
  
  CONCLUSIONS
  Among patients with non-small-cell lung cancer who receive erlotinib, the presence of an EGFR mutation may increase responsiveness to the agent, but it is not indicative of a survival benefit.
authors: University Health Network, Princess Margaret Hospital Site, and the Ontario Cancer Institute, University of Toronto, Canada.
authors: Ming-Sound
authors: MS
authors: Tsao
authors: Akira
authors: A
authors: Sakurada
authors: Jean-Claude
authors: JC
authors: Cutz
authors: Chang-Qi
authors: CQ
authors: Zhu
authors: Suzanne
authors: S
authors: Kamel-Reid
authors: Jeremy
authors: J
authors: Squire
authors: Ian
authors: I
authors: Lorimer
authors: Tong
authors: T
authors: Zhang
authors: Ni
authors: N
authors: Liu
authors: Manijeh
authors: M
authors: Daneshmand
authors: Paula
authors: P
authors: Marrano
authors: Gilda
authors: G
authors: da Cunha Santos
authors: Alain
authors: A
authors: Lagarde
authors: Frank
authors: F
authors: Richardson
authors: Lesley
authors: L
authors: Seymour
authors: Marlo
authors: M
authors: Whitehead
authors: Keyue
authors: K
authors: Ding
authors: Joseph
authors: J
authors: Pater
authors: Frances A
authors: FA
authors: Shepherd
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors