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.
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 NSCLCpatients. 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.
Authors: Lynette M Sholl; Yun Xiao; Victoria Joshi; Beow Y Yeap; Leigh-Anne Cioffredi; David M Jackman; Charles Lee; Pasi A Jänne; Neal I Lindeman Journal: Am J Clin Pathol Date: 2010-06 Impact factor: 2.493
Authors: Elizabeth A Hopper-Borge; Rochelle E Nasto; Vladimir Ratushny; Louis M Weiner; Erica A Golemis; Igor Astsaturov Journal: Expert Opin Ther Targets Date: 2009-03 Impact factor: 6.902
Authors: Alison L Van Dyke; Michele L Cote; Geoffrey M Prysak; Gina B Claeys; Angie S Wenzlaff; Valerie C Murphy; Fulvio Lonardo; Ann G Schwartz Journal: Carcinogenesis Date: 2008-05-02 Impact factor: 4.944