title: Association of EGFR expression level and cetuximab activity in patient-derived xenograft models of human non-small cell lung cancer.
abstract: OBJECTIVE
  To explore in a panel of patient-derived xenograft models of human non-small cell lung cancer (NSCLC) whether high EGFR expression, was associated with cetuximab activity.
  
  
  METHODS
  NSCLC patient-derived xenograft models (n=45) were implanted subcutaneously into panels of nude mice and randomization cohorts were treated with either cetuximab, cisplatin, cisplatin plus cetuximab, vehicle control, or else were left untreated. Responses according to treatment were assessed at week 3 by analyzing the relative change in tumor volume and an experimental analogue of the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. An EGFR IHC score was calculated for each patient-derived xenograft model and response was assessed according to EGFR expression level.
  
  
  RESULTS
  When tumors were stratified into high and low EGFR expression groups (IHC score threshold 200; scale 0-300), a stronger antitumor activity was seen in the high EGFR expression group compared with the low EGFR expression group in both the cetuximab monotherapy and cisplatin plus cetuximab combination therapy settings. For tumors treated with cisplatin plus cetuximab, the objective response rate was significantly higher in the high EGFR expression group compared with the low EGFR expression group (68% vs. 29%). Objective response rates were similar in high and low expression groups for tumors treated with cisplatin alone (27% vs. 24%, respectively).
  
  
  CONCLUSIONS
  Cetuximab activity in NSCLC patient-derived xenograft models was demonstrated clearly only in tumors that expressed high levels of EGFR, as defined by an IHC score of ≥200.
authors.affiliation: Merck KGaA, Darmstadt, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Amendt
authors.affiliation: Merck KGaA, Darmstadt, Germany.
authors.forename: Eike
authors.initials: E
authors.lastname: Staub
authors.affiliation: Merck KGaA, Darmstadt, Germany.
authors.forename: Manja
authors.initials: M
authors.lastname: Friese-Hamim
authors.affiliation: Institute of Pathology, University of Witten/Herdecke and HELIOS Hospital Wuppertal, Wuppertal, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Störkel
authors.affiliation: Merck KGaA, Darmstadt, Germany. christopher.stroh@merckgroup.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Stroh
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000068818:Cetuximab; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab