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Annals of Oncology Advance Access originally published online on April 25, 2005
Annals of Oncology 2005 16(7):1081-1086; doi:10.1093/annonc/mdi221
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© 2005 European Society for Medical Oncology

Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients

H. Cortes-Funes1, C. Gomez2, R. Rosell3,*, P. Valero4, C. Garcia-Giron5, A. Velasco6, A. Izquierdo7, P. Diz8, C. Camps9, D. Castellanos1, V. Alberola10, F. Cardenal11, J. L. Gonzalez-Larriba12, J. M. Vieitez13, I. Maeztu14, J. J. Sanchez15, C. Queralt3, C. Mayo3, P. Mendez3, T. Moran3, M. Taron3 On behalf of the Spanish Lung Cancer Group

1 Hospital Doce de Octubre, Madrid; 2 Xeral Cies de Vigo, Vigo; 3 Catalan Institute of Oncology, Badalona; 4 Clinica Sagrado Corazon, Sevilla; 5 Hospital General Yague, Burgos; 6 Hospital La Princesa, Madrid; 7 Catalan Institute of Oncology, Girona; 8 Hospital de Leon, Leon; 9 Hospital General de Valencia, Valencia; 10 Hospital Arnau de Vilanova, Valencia; 11 Catalan Insitute of Oncology, Bellvitge; 12 Hospital Clinico San Carlos, Madrid; 13 Hospital General de Asturias, Oviedo; 14 Hospital Alcoy, Alicante; 15 Autonomous University of Madrid, Madrid, Spain

* Correspondence to: Dr R. Rosell, MD, Chief, Medical Oncology Service, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet, s/n, 08916 Badalona, Barcelona, Spain. Tel: +34-93-497-89-25; Fax: +34-93-497-89-50; Email: rrosell{at}ns.hugtip.scs.es

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.

Patients and 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.

Key words: EGFR, gefitinib, mutations, NSCLC, predictive markers


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