title: A multicentre phase II gene expression profiling study of putative relationships between tumour biomarkers and clinical response with erlotinib in non-small-cell lung cancer.
abstract: BACKGROUND
  Identification of appropriate markers for predicting clinical benefit with erlotinib in non-small-cell lung cancer (NSCLC) may be able to guide patient selection for treatment. This open-label, multicentre, phase II trial aimed to identify genes with potential use as biomarkers for clinical benefit from erlotinib therapy.
  
  
  METHODS
  Adults with stage IIIb/IV NSCLC in whom one or more chemotherapy regimen had failed were treated with erlotinib (150 mg/day). Tumour biopsies were analysed using gene expression profiling with Affymetrix GeneChip microarrays. Differentially expressed genes were verified using quantitative RT-PCR (qRT-PCR).
  
  
  RESULTS
  A total of 264 patients were enrolled in the study. Gene expression profiles found no statistically significant differentially expressed genes between patients with and without clinical benefit. In an exploratory analysis in responding versus nonresponding patients, three genes on chromosome 7 were expressed at higher levels in the responding group [epidermal growth factor receptor (EGFR), phosphoserine phosphatase (PSPH) and Rap guanine nucleotide exchange factor 5 (RAPGEF5)]. Independent quantification using qRT-PCR validated the association between EGFR and PSPH overexpression, but not RAPGEF5 overexpression, and clinical outcome.
  
  
  CONCLUSIONS
  This study supports the use of erlotinib as an alternative to chemotherapy for patients with relapsed advanced NSCLC. Genetic amplification of the EGFR region of chromosome 7 may be associated with response to erlotinib therapy.
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: E-H
authors.initials: EH
authors.lastname: Tan
authors.affiliation: Department of Oncology, Regional Lung Disease Centre, Poznan.
authors.forename: R
authors.initials: R
authors.lastname: Ramlau
authors.affiliation: Oncological Chemotherapy Clinic, Regional Oncology Centre, Lodz, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Pluzanska
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan.
authors.forename: H-P
authors.initials: HP
authors.lastname: Kuo
authors.affiliation: Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Reck
authors.affiliation: Department of Pneumology, Oncology and Allergology, Akademia Medyczna w Lublinie, Lublin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Milanowski
authors.affiliation: Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong.
authors.forename: J S-K
authors.initials: JS
authors.lastname: Au
authors.affiliation: Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Felip
authors.affiliation: Department of Internal Medicine and Department of Emergency Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: P-C
authors.initials: PC
authors.lastname: Yang
authors.affiliation: Specialized Hospital for Active Treatment in Oncology, Sofia, Bulgaria.
authors.forename: D
authors.initials: D
authors.lastname: Damyanov
authors.affiliation: Laboratory of Thoracic Oncology, Research Institute of Pulmonology, Pavlov State Medical University, Saint Petersburg, Russia.
authors.forename: S
authors.initials: S
authors.lastname: Orlov
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Akimov
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Delmar
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Essioux
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Hillenbach
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Klughammer
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: McLoughlin
authors.affiliation: Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. Electronic address: jbaselga@vhebron.net.
authors.forename: J
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride