title: Screening for epidermal growth factor receptor mutations in lung cancer.
abstract: BACKGROUND
  Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non-small-cell lung cancer. We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment.
  
  
  METHODS
  From April 2005 through November 2008, lung cancers from 2105 patients in 129 institutions in Spain were screened for EGFR mutations. The analysis was performed in a central laboratory. Patients with tumors carrying EGFR mutations were eligible for erlotinib treatment.
  
  
  RESULTS
  EGFR mutations were found in 350 of 2105 patients (16.6%). Mutations were more frequent in women (69.7%), in patients who had never smoked (66.6%), and in those with adenocarcinomas (80.9%) (P<0.001 for all comparisons). The mutations were deletions in exon 19 (62.2%) and L858R (37.8%). Median progression-free survival and overall survival for 217 patients who received erlotinib were 14 months and 27 months, respectively. The adjusted hazard ratios for the duration of progression-free survival were 2.94 for men (P<0.001); 1.92 for the presence of the L858R mutation, as compared with a deletion in exon 19 (P=0.02); and 1.68 for the presence of the L858R mutation in paired serum DNA, as compared with the absence of the mutation (P=0.02). The most common adverse events were mild rashes and diarrhea; grade 3 cutaneous toxic effects were recorded in 16 patients (7.4%) and grade 3 diarrhea in 8 patients (3.7%).
  
  
  CONCLUSIONS
  Large-scale screening of patients with lung cancer for EGFR mutations is feasible and can have a role in decisions about treatment.
authors.affiliation: Catalan Institute of Oncology and Autonomous University of Barcelona, Hospital Germans Trias i Pujol, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Teresa
authors.initials: T
authors.lastname: Moran
authors.forename: Cristina
authors.initials: C
authors.lastname: Queralt
authors.forename: Rut
authors.initials: R
authors.lastname: Porta
authors.forename: Felipe
authors.initials: F
authors.lastname: Cardenal
authors.forename: Carlos
authors.initials: C
authors.lastname: Camps
authors.forename: Margarita
authors.initials: M
authors.lastname: Majem
authors.forename: Guillermo
authors.initials: G
authors.lastname: Lopez-Vivanco
authors.forename: Dolores
authors.initials: D
authors.lastname: Isla
authors.forename: Mariano
authors.initials: M
authors.lastname: Provencio
authors.forename: Amelia
authors.initials: A
authors.lastname: Insa
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Massuti
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Gonzalez-Larriba
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: Isabel
authors.initials: I
authors.lastname: Bover
authors.forename: Rosario
authors.initials: R
authors.lastname: Garcia-Campelo
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Moreno
authors.forename: Silvia
authors.initials: S
authors.lastname: Catot
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.forename: Noemi
authors.initials: N
authors.lastname: Reguart
authors.forename: Ramon
authors.initials: R
authors.lastname: Palmero
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Sánchez
authors.forename: Roman
authors.initials: R
authors.lastname: Bastus
authors.forename: Clara
authors.initials: C
authors.lastname: Mayo
authors.forename: Jordi
authors.initials: J
authors.lastname: Bertran-Alamillo
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Molina
authors.forename: Jose Javier
authors.initials: JJ
authors.lastname: Sanchez
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D017678:Sex Distribution; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors