Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer.
Authors
Hirsch, Fred RVarella-Garcia, Marileila
Bunn, Paul A
Franklin, Wilbur A
Dziadziuszko, Rafal
Thatcher, Nick
Chang, Alex
Parikh, Purvish
Pereira, José Rodrigues
Ciuleanu, Tudor
Von Pawel, J
Watkins, Claire
Flannery, Angela
Ellison, Gillian
Donald, Emma
Knight, Lucy
Parums, Dinah V
Botwood, Nicholas
Holloway, Brian
Affiliation
University of Colorado Cancer Center, PO Box 6511, Mail Stop 8111, Aurora, CO 80045, USA. Fred.Hirsch@UCHSC.eduIssue Date
2006-11-01
Metadata
Show full item recordAbstract
PURPOSE: The phase III Iressa Survival Evaluation in Lung Cancer (ISEL) trial compared gefitinib with placebo in 1,692 patients with refractory advanced non-small-cell lung cancer. We analyzed ISEL tumor biopsy samples to examine relationships between biomarkers and clinical outcome after gefitinib treatment in a placebo-controlled setting. METHODS: Biomarkers included epidermal growth factor receptor (EGFR) gene copy number by fluorescence in situ hybridization (n = 370); EGFR (n = 379) and phosphorylated Akt (p-Akt) protein expression (n = 382) by immunohistochemistry; and mutations in EGFR (n = 215), KRAS (n = 152), and BRAF (n = 118). RESULTS: High EGFR gene copy number was a predictor of a gefitinib-related effect on survival (hazard ratio [HR], 0.61 for high copy number and HR, 1.16 for low copy number; comparison of high v low copy number HR, P = .045). EGFR protein expression was also related to clinical outcome (HR for positive, 0.77; HR for negative, 1.57; comparison of high v low protein expression HR, P = .049). Patients with EGFR mutations had higher response rates than patients without EGFR mutations (37.5% v 2.6%); there were insufficient data for survival analysis. No relationship was observed between p-Akt protein expression and survival outcome, and the limited amount of data collected for KRAS and BRAF mutations prevented any meaningful evaluation of clinical outcomes in relation to these mutations. CONCLUSION: EGFR gene copy number was a predictor of clinical benefit from gefitinib in ISEL. Additional studies are warranted to assess these biomarkers fully for the identification of patients most likely to benefit from gefitinib treatment.Citation
Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. 2006, 24 (31):5034-42 J. Clin. Oncol.Journal
Journal of Clinical OncologyDOI
10.1200/JCO.2006.06.3958PubMed ID
17075123Type
ArticleLanguage
enISSN
1527-7755ae974a485f413a2113503eed53cd6c53
10.1200/JCO.2006.06.3958