Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib

F. R. Hirsch, M. Varella-Garcia, F. Cappuzzo, J. McCoy, L. Bemis, A. C. Xavier, R. Dziadziuszko, P. Gumerlock, K. Chansky, H. West, A. F. Gazdar, L. Crino, D. R. Gandara, W. A. Franklin, Paul A. Bunn

Research output: Contribution to journalArticle

254 Scopus citations

Abstract

Background: Biological markers for optimal selection of patient to epidermal growth factor receptor (EGFR)-targeted therapies are not established in advanced non-small-cell lung cancer (NSCLC). Patients and methods: EGFR/HER2 gene copy number by FISH, EGFR protein and pAKT expression by immunohistochemistry (IHC) and EGFR and KRAS mutations were tested in 204 gefitinib-treated NSCLC patients. Results: Increased EGFR and HER2 gene copy number (FISH+), EGFR protein overexpression (IHC+), EGFR mutations and pAKT overexpression were all associated with significantly higher response rates (33%, 29%, 22%, 39% and 20% respectively). EGFR FISH+ (32%) and IHC+ (61%) correlated with improved survival, while EGFR mutations (27%), KRAS mutations (26%) and pAKT expression (69%) did not. In multivariate survival analysis EGFR FISH and IHC were independent predictive markers. EGFR FISH+/IHC+ patients (23%) had a median survival of 21 months versus 6 months for double-negative patients (30%). Conclusion: Combination of EGFR FISH and IHC is effective predictor for benefit from gefitinib. Patients with double-negative results are unlikely to benefit in western NSCLC populations.

Original languageEnglish (US)
Pages (from-to)752-760
Number of pages9
JournalAnnals of Oncology
Volume18
Issue number4
DOIs
StatePublished - Apr 1 2007

Keywords

  • Epidermal growth factor receptor
  • Gefitinib
  • Gene copy number
  • Non-small-cell lung cancer
  • Protein expression

ASJC Scopus subject areas

  • Hematology
  • Oncology

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    Hirsch, F. R., Varella-Garcia, M., Cappuzzo, F., McCoy, J., Bemis, L., Xavier, A. C., Dziadziuszko, R., Gumerlock, P., Chansky, K., West, H., Gazdar, A. F., Crino, L., Gandara, D. R., Franklin, W. A., & Bunn, P. A. (2007). Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib. Annals of Oncology, 18(4), 752-760. https://doi.org/10.1093/annonc/mdm003