Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients.
BACKGROUND
North American and Japanese non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activation via tyrosine kinase (TK) mutations respond dramatically to gefitinib treatment. To date, however, the frequency and effect of EGFR TK mutations have not been examined in European patients.


METHODS
Eighty-three Spanish advanced NSCLC patients who had progressed after chemotherapy, were treated with compassionate use of gefitinib. Patients were selected on the basis of available tumor tissue. Tumor genomic DNA was retrieved from paraffin-embedded tissue obtained by laser capture microdissection. EGFR mutations in exons 19 and 21 were examined by direct sequencing.


RESULTS
EGFR mutations were found in 10 of 83 (12%) of patients. All mutations were found in adenocarcinomas, more frequently in females (P=0.007) and non-smokers (P=0.01). Response was observed in 60% of patients with mutations and 8.8% of patients with wild-type EGFR (P=0.001). Time to progression for patients with mutations was 12.3 months, compared with 3.6 months for patients with wild-type EGFR (P=0.002). Median survival was 13 months for patients with mutations and 4.9 months for those with wild-type EGFR (P=0.02).


CONCLUSIONS
EGFR TK mutational analysis is a novel predictive test for selecting lung adenocarcinoma patients for targeted therapy with EGFR TK inhibitors.
Cortes-Funes
H
H
Hospital Doce de Octubre, Madrid, Spain.
Gomez
C
C
Rosell
R
R
Valero
P
P
Garcia-Giron
C
C
Velasco
A
A
Izquierdo
A
A
Diz
P
P
Camps
C
C
Castellanos
D
D
Alberola
V
V
Cardenal
F
F
Gonzalez-Larriba
J L
JL
Vieitez
J M
JM
Maeztu
I
I
Sanchez
J J
JJ
Queralt
C
C
Mayo
C
C
Mendez
P
P
Moran
T
T
Taron
M
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017931:DNA Primers; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D013030:Spain; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D017931:DNA Primers; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib