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
Journal
Annals of Oncology
Journal Volume
21
Journal Issue
2
Pages
217-222
Date Issued
2010
Author(s)
Tan E.-H.
Ramlau R.
Pluzanska A.
Kuo H.-P.
Reck M.
Milanowski J.
Au J.S.-K.
Felip E.
Damyanov D.
Orlov S.
Akimov M.
Delmar P.
Essioux L.
Hillenbach C.
Klughammer B.
McLoughlin P.
Baselga J.
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. ? The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
Subjects
Biomarkers; Epidermal growth factor receptor; Erlotinib; Gene expression; Non-small-cell lung cancer; PCR
SDGs
Other Subjects
beta 2 microglobulin; biological marker; epidermal growth factor receptor; erlotinib; guanine nucleotide exchange factor; hypoxanthine phosphoribosyltransferase; K ras protein; phosphatase; phosphoserine phosphatase; Rap guanine nucleotide exchange factor; RNA; unclassified drug; adult; aged; article; Asian; cancer relapse; cancer staging; Caucasian; chromosome 7; cigarette smoking; clinical trial; controlled study; drug efficacy; drug safety; drug treatment failure; ethnic difference; female; fluorescence in situ hybridization; gene amplification; gene expression profiling; gene identification; gene overexpression; human; laser capture microdissection; lung non small cell cancer; major clinical study; male; microarray analysis; multicenter study; patient selection; phase 2 clinical trial; prediction; priority journal; reverse transcription polymerase chain reaction; treatment response; tumor biopsy
Type
journal article