title: High EGFR gene copy number and skin rash as predictive markers for EGFR tyrosine kinase inhibitors in patients with advanced squamous cell lung carcinoma.
abstract: OBJECTIVE
  This study aimed to search for predictors of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) efficacy in previously treated patients with advanced squamous cell lung carcinoma in which EGFR mutations are very rare.
  
  
  METHODS
  EGFR gene copy numbers were assessed by FISH and evaluated as predictors of EGFR-TKI efficacy in 71 patients with advanced squamous cell lung cancer who received gefitinib or erlotinib as a second-line or higher therapy. The tumors were classified into EGFR/FISH-positive (high polysomy/gene amplification) and EGFR/FISH-negative (other) groups.
  
  
  RESULTS
  EGFR/FISH was positive in 19 (26.7%) patients. Only EGFR/FISH positive status was correlated with the EGFR-TKIs response (EGFR/FISH(+) vs. EGFR/FISH(-), 26.3% vs. 2.0%; P = 0.005). In a multivariate analysis, the risk of progression was lower in EGFR/FISH-positive patients (HR of EGFR/FISH(+) vs. EGFR/FISH(-), 0.57; P = 0.057) or patients experiencing grade 2 or more rash (HR for rash grade 2 or more vs. less than 2, 0.54; P = 0.042), compared with EGFR/FISH-negative patients or those experiencing grade of less than 2 rash, respectively. When the combined criteria of EGFR/FISH and skin rash severity were analyzed, EGFR/FISH-negative patients with grade less than 2 rash had poorer clinical outcomes than patients with positive EGFR/FISH or grade 2 or more rash, apparent as a lower response rate (0.0% vs. 21.4%; P = 0.003) and a shorter median progression-free survival (1.13 months vs. 3.90 months; P = 0.0002).
  
  
  CONCLUSIONS
  EGFR/FISH and skin rash severity may be used to identify which patients are likely to gain a benefit from EGFR-TKIs in this population.
authors.affiliation: Center for Lung Cancer, National Cancer Center, Goyang, Korea.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Lee
authors.forename: Hyo Sup
authors.initials: HS
authors.lastname: Shim
authors.forename: Moo Suk
authors.initials: MS
authors.lastname: Park
authors.forename: Joo-Hang
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005076:Exanthema / Q000150:complications*; D005260:Female; D018628:Gene Dosage; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019233:Retreatment
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors