Annals of Oncology Advance Access originally published online on February 22, 2007
Annals of Oncology 2007 18(4):752-760; doi:10.1093/annonc/mdm003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2007 European Society for Medical Oncology
lung cancer |
Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib
1 Division of Medical Oncology
2 Division of Pathology, Department of Medicine, University of Colorado Health Sciences Center and University of Colorado Cancer Center, Aurora, CO, USA
3 Bellaria Hospital, Div. of Medical Oncology, Via Altura 3, 40139 Bologna, Italy
4 Southwest Oncology Group, 1730 Minor Ave, Ste 1900, Seattle, WA 98101-1468, USA
5 Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-8593, USA
* Correspondence to: Dr P. A. Bunn Jr, University of Colorado Cancer Center, PO Box 6511, Mail Stop 8117, Aurora, CO 80010, USA. Tel: +1-303-724-3155; Fax: +1-303-724-3162; E-mail: paul.bunn{at}uchsc.edu
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.
Key words: epidermal growth factor receptor, gefitinib, gene copy number, non-small-cell lung cancer, protein expression
Received for publication August 28, 2006. Revision received November 9, 2006. Accepted for publication January 5, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Lara-Guerra, T. K. Waddell, M. A. Salvarrey, A. M. Joshua, C. T. Chung, N. Paul, S. Boerner, A. Sakurada, O. Ludkovski, C. Ma, et al. Phase II Study of Preoperative Gefitinib in Clinical Stage I Non-Small-Cell Lung Cancer J. Clin. Oncol., December 20, 2009; 27(36): 6229 - 6236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Azzoli, S. Baker Jr, S. Temin, W. Pao, T. Aliff, J. Brahmer, D. H. Johnson, J. L. Laskin, G. Masters, D. Milton, et al. American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer J. Clin. Oncol., December 20, 2009; 27(36): 6251 - 6266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Laurent-Puig, A. Cayre, G. Manceau, E. Buc, J.-B. Bachet, T. Lecomte, P. Rougier, A. Lievre, B. Landi, V. Boige, et al. Analysis of PTEN, BRAF, and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer J. Clin. Oncol., December 10, 2009; 27(35): 5924 - 5930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Peled, K. Yoshida, M. W. Wynes, and F. R. Hirsch Review: Predictive and prognostic markers for epidermal growth factor receptor inhibitor therapy in non-small cell lung cancer Therapeutic Advances in Medical Oncology, November 1, 2009; 1(3): 137 - 144. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Ray, R. Salgia, and E. E. Vokes The Role of EGFR Inhibition in the Treatment of Non-Small Cell Lung Cancer Oncologist, November 1, 2009; 14(11): 1116 - 1130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. PESEK, L. BENESOVA, B. BELSANOVA, P. MUKENSNABL, F. BRUHA, and M. MINARIK Dominance of EGFR and Insignificant KRAS Mutations in Prediction of Tyrosine-kinase Therapy for NSCLC Patients Stratified by Tumor Subtype and Smoking Status Anticancer Res, July 1, 2009; 29(7): 2767 - 2773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Riely, J. Marks, and W. Pao KRAS Mutations in Non-Small Cell Lung Cancer Proceedings of the ATS, April 15, 2009; 6(2): 201 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Pennell and T. J. Lynch Jr. Combined Inhibition of the VEGFR and EGFR Signaling Pathways in the Treatment of NSCLC Oncologist, April 1, 2009; 14(4): 399 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Pantaleo, M. Nannini, A. Maleddu, S. Fanti, C. Nanni, S. Boschi, F. Lodi, G. Nicoletti, L. Landuzzi, P. L. Lollini, et al. Experimental results and related clinical implications of PET detection of epidermal growth factor receptor (EGFr) in cancer Ann. Onc., February 1, 2009; 20(2): 213 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Riely and M. Ladanyi KRAS Mutations: An Old Oncogene Becomes a New Predictive Biomarker J. Mol. Diagn., November 1, 2008; 10(6): 493 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-Q. Zhu, G. da Cunha Santos, K. Ding, A. Sakurada, J.-C. Cutz, N. Liu, T. Zhang, P. Marrano, M. Whitehead, J. A. Squire, et al. Role of KRAS and EGFR As Biomarkers of Response to Erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21 J. Clin. Oncol., September 10, 2008; 26(26): 4268 - 4275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Van Dyke, M. L. Cote, G. M. Prysak, G. B. Claeys, A. S. Wenzlaff, V. C. Murphy, F. Lonardo, and A. G. Schwartz COX-2/EGFR expression and survival among women with adenocarcinoma of the lung Carcinogenesis, September 1, 2008; 29(9): 1781 - 1787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Hirsch, R. S. Herbst, C. Olsen, K. Chansky, J. Crowley, K. Kelly, W. A. Franklin, P. A. Bunn Jr, M. Varella-Garcia, and D. R. Gandara Increased EGFR Gene Copy Number Detected by Fluorescent In Situ Hybridization Predicts Outcome in Non-Small-Cell Lung Cancer Patients Treated With Cetuximab and Chemotherapy J. Clin. Oncol., July 10, 2008; 26(20): 3351 - 3357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Weiss, L. T. Bemis, E. Nakajima, M. Sugita, D. K. Birks, W. A. Robinson, M. Varella-Garcia, P. A. Bunn Jr, J. Haney, B. A. Helfrich, et al. EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines Ann. Onc., June 1, 2008; 19(6): 1053 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. L. Keedy, C. L. Arteaga, and D. H. Johnson Does Gefitinib Shorten Lung Cancer Survival? Chaos Redux J. Clin. Oncol., May 20, 2008; 26(15): 2428 - 2430. [Full Text] [PDF]
|
|
|
|
 |
|
 G D Smith, B E Chadwick, C Willmore-Payne, and J S Bentz Detection of epidermal growth factor receptor gene mutations in cytology specimens from patients with non-small cell lung cancer utilising high-resolution melting amplicon analysis J. Clin. Pathol., April 1, 2008; 61(4): 487 - 493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Peipp, T. Schneider-Merck, M. Dechant, T. Beyer, J. J. Lammerts van Bueren, W. K. Bleeker, P. W. H. I. Parren, J. G. J. van de Winkel, and T. Valerius Tumor Cell Killing Mechanisms of Epidermal Growth Factor Receptor (EGFR) Antibodies Are Not Affected by Lung Cancer-Associated EGFR Kinase Mutations J. Immunol., March 15, 2008; 180(6): 4338 - 4345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. McDermott, S. V. Sharma, L. Dowell, P. Greninger, C. Montagut, J. Lamb, H. Archibald, R. Raudales, A. Tam, D. Lee, et al. Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling PNAS, December 11, 2007; 104(50): 19936 - 19941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Forastiere and B. A. Burtness Epidermal Growth Factor Receptor Inhibition in Head and Neck Cancer--More Insights, but More Questions J. Clin. Oncol., June 1, 2007; 25(16): 2152 - 2155. [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Frederick, B. A. Helfrich, C. D. Coldren, D. Zheng, D. Chan, P. A. Bunn Jr., and D. Raben Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma Mol. Cancer Ther., June 1, 2007; 6(6): 1683 - 1691. [Abstract] [Full Text] [PDF]
|
|