title: Somatic EGFR mutation and gene copy gain as predictive biomarkers for response to tyrosine kinase inhibitors in non-small cell lung cancer.
abstract: OBJECTIVE
  The aim of this systematic review and meta-analysis was to characterize common EGFR molecular aberrations as potential predictive biomarkers for response to monotherapy with tyrosine kinase inhibitors (TKI) in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We systematically identified articles investigating EGFR status [somatic mutational and gene copy aberrations (copy number)] in patients with NSCLC treated with TKIs. Eligible studies had to report complete and partial response rates stratified by EGFR status. We used random effects models for bivariable meta-analysis of sensitivity and specificity; positive and negative likelihood ratios (+LR and -LR, respectively) were also calculated and were considered as secondary end points.
  
  
  RESULTS
  Among 222 retrieved articles, 59 were considered eligible for the somatic EGFR mutation meta-analysis (1,020 mutations among 3,101 patients) and 21 were considered eligible for the EGFR gene copy number meta-analysis (542 gene gain among 1,539 patients). EGFR mutations were predictive of response to single-agent TKIs [sensitivity, 0.78; 95% confidence interval (95% CI), 0.74-0.82; specificity, 0.86; 95% CI, 0.82-0.89; +LR, 5.6; -LR, 0.25]. EGFR gene gain was also associated with response to TKIs, albeit with lower sensitivity and specificity. In subgroup analysis, the only recognized trend was for a higher predictive value in Whites compared with East Asians for both mutation and gene copy number.
  
  
  CONCLUSIONS
  This analysis provides empirical evidence that EGFR mutations are sensitive and specific predictors of response to single-agent epidermal growth factor receptor TKIs in advanced NSCLC. The diagnostic performance of mutations seems better than that of EGFR gene gain.
authors.affiliation: Department of Pathophysiology, Medical School, National University of Athens, Athens, Greece.
authors.forename: Issa J
authors.initials: IJ
authors.lastname: Dahabreh
authors.forename: Helena
authors.initials: H
authors.lastname: Linardou
authors.forename: Fotios
authors.initials: F
authors.lastname: Siannis
authors.forename: Paris
authors.initials: P
authors.lastname: Kosmidis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Bafaloukos
authors.forename: Samuel
authors.initials: S
authors.lastname: Murray
mesh_terms: D015415:Biomarkers; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors