title: An open label phase II study evaluating first-line EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer patients with tumors showing high EGFR gene copy number.
abstract: BACKGROUND
  First-line treatment with epidermal growth factor receptor (EGFR) inhibitors in NSCLC is effective in patients with activating EGFR mutations. The activity of erlotinib in patients harboring high EGFR gene copy number has been considered debatable.
  
  
  METHODS
  A multicenter, open-label, single-arm phase II clinical trial was performed to test the efficacy of erlotinib in the first-line treatment of NSCLC patients harboring high EGFR gene copy number defined as ≥4 copies in ≥40% of cells.
  
  
  RESULTS
  Between December 2007 and April 2011, tumor samples from 149 subjects were screened for EGFR gene copy number by fluorescence in-situ hybridization (FISH), Out of 49 patients with positive EGFR FISH test, 45 were treated with erlotinib. Median PFS in the intent-to-treat population was 3.3 months (95%CI: 1.8-3.9 months), and median overall survival was 7.9 months (95% CI: 5.1-12.6 months). Toxicity profile of erlotinib was consistent with its known safety profile. The trial was stopped prematurely at 63% of originally planned sample size due to accumulating evidence that EGFR gene copy number should not be used to select NSCLC patients to first-line therapy with EGFR TKI. Data on erlotinib efficacy according to EGFR, KRAS and BRAF mutations are additionally presented.
  
  
  CONCLUSIONS
  This trial argues against using high gene copy number for selection of NSCLC patients to first-line therapy with EGFR TKIs. The study adds to the discussion on efficacy of other targeted agents in patients with target gene amplified tumors.
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdańsk, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Szutowicz-Zielińska
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdańsk, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Konopa
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdańsk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kowalczyk
authors.affiliation: Department of Oncology, The Centre for Pulmonary Diseases Olsztyn, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Suszko-Każarnowicz
authors.affiliation: Department of Oncology, Military Institute of Medicine, Warsaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Duchnowska
authors.affiliation: Department of Lung Diseases, Mazovian Centre for Treatment of Lung Diseases and Tuberculosis, Otwock, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szczęsna
authors.affiliation: Department of Biology and Genetics, Medical University of Gdańsk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ratajska
authors.affiliation: Roche, Warszawa, Poland.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Sowa
authors.affiliation: Department of Biology and Genetics, Medical University of Gdańsk, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Limon
authors.affiliation: Department of Pathomorphology, Medical University of Gdańsk, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.affiliation: Interuniversity Institute of Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek, Belgium.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Burzykowski
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdańsk, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdańsk, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Dziadziuszko
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D003967:Diarrhea / Q000139:chemically induced; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: epidermal growth factor receptor; erlotinib; gene copy number; non-small cell lung cancer