title: Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) gene copy number detected by fluorescent in situ hybridization (FISH) has proven to be useful for selection of non-small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine kinase inhibitors. Here, we evaluate EGFR FISH as a predictive marker in NSCLC patients receiving the EGFR monoclonal antibody inhibitor cetuximab plus chemotherapy.
  
  
  METHODS
  Two hundred twenty-nine chemotherapy-naive patients with advanced-stage NSCLC were enrolled onto a phase II selection trial evaluating sequential or concurrent chemotherapy (paclitaxel plus carboplatin) with cetuximab.
  
  
  RESULTS
  EGFR FISH was assessable in 76 patients with available tumor tissue and classified as positive (four or more gene copies per cell in >/= 40% of the cells or gene amplification) in 59.2%. Response (complete response/partial response) was numerically higher in FISH-positive (45%) versus FISH-negative (26%) patients (P = .14), whereas disease control rate (complete response/partial response plus stable disease) was statistically superior (81% v 55%, respectively; P = .02). Patients with FISH-positive tumors had a median progression-free survival time of 6 months compared with 3 months for FISH-negative patients (P = .0008). Median survival time was 15 months for the FISH-positive group compared with 7 months for patients who were FISH negative. (P = .04). Furthermore, survival favored FISH-positive patients receiving concurrent therapy.
  
  
  CONCLUSIONS
  These results are the first to suggest that EGFR FISH is a predictive factor for selection of NSCLC patients for cetuximab plus chemotherapy. Prospective validation of these findings is warranted.
authors.affiliation: Southwest Oncology Group, San Antonio, USA. Fred.Hirsch@UCHSC.edu
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.forename: Christine
authors.initials: C
authors.lastname: Olsen
authors.forename: Kari
authors.initials: K
authors.lastname: Chansky
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Karen
authors.initials: K
authors.lastname: Kelly
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Franklin
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bunn
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000068818:Cetuximab; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D018579:Patient Selection; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012016:Reference Values; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068818:Cetuximab