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

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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

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erbB-1 Genes
Gene Dosage
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Immunohistochemistry
Proteins
erbB-2 Genes
Mutation
gefitinib
Survival
Survival Analysis
Patient Selection
Multivariate Analysis
Biomarkers

Keywords

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

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

In: Annals of Oncology, Vol. 18, No. 4, 01.04.2007, p. 752-760.

Research output: Contribution to journalArticle

Hirsch, FR, Varella-Garcia, M, Cappuzzo, F, McCoy, J, Bemis, L, Xavier, AC, Dziadziuszko, R, Gumerlock, P, Chansky, K, West, H, Gazdar, AF, Crino, L, Gandara, DR, Franklin, WA & Bunn, PA 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, vol. 18, no. 4, pp. 752-760. https://doi.org/10.1093/annonc/mdm003
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, Paul A. / Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib. In: Annals of Oncology. 2007 ; Vol. 18, No. 4. pp. 752-760.
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title = "Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib",
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.",
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AU - Hirsch, F. R.

AU - Varella-Garcia, M.

AU - Cappuzzo, F.

AU - McCoy, J.

AU - Bemis, L.

AU - Xavier, A. C.

AU - Dziadziuszko, R.

AU - Gumerlock, P.

AU - Chansky, K.

AU - West, H.

AU - Gazdar, A. F.

AU - Crino, L.

AU - Gandara, D. R.

AU - Franklin, W. A.

AU - Bunn, Paul A.

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N2 - 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.

AB - 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.

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