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


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%).


CONCLUSIONS
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.
Hirsch
F R
FR
Division of Medical Oncology, Department of Medicine, University of Colorado Health Sciences Center and Cancer Center, Aurora, CO 80010, USA.
Varella-Garcia
M
M
Cappuzzo
F
F
McCoy
J
J
Bemis
L
L
Xavier
A C
AC
Dziadziuszko
R
R
Gumerlock
P
P
Chansky
K
K
West
H
H
Gazdar
A F
AF
Crino
L
L
Gandara
D R
DR
Franklin
W A
WA
Bunn
P A
PA
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D018628:Gene Dosage; D018734:Genes, erbB-2; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D016896:Treatment Outcome
D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib