Setting the benchmark for tailoring treatment with EGFR tyrosine kinase inhibitors.
Overexpression and mutational activation of the epidermal growth factor receptor (EGFR) is involved in tumor development and progression in non-small-cell lung cancer (NSCLC). Somatic mutations in the EGFR kinase domain confer high sensitivity to tyrosine kinase inhibitors (TKIs). The two most frequent mutations are the exon 19 deletion and the exon 21 L858R. Distinct EGFR mutations differ in their effect on response and survival to TKIs. We have examined EGFR mutations in more than 1800 stage IV NSCLCs for erlotinib customization as both first- and second-line treatment. EGFR mutations cluster in never-smokers, women and adenocarcinomas, as has been described in multiple retrospective studies. The overall frequency of EGFR mutations in our study was 15% and the response in first- and second-line treatment was 84%. Overall, progression-free survival was 13 months and median survival has not been reached. However, patients with exon 19 deletions showed a significantly longer progression-free survival than those harboring L858R mutations. Despite abundant molecular evidence on the role of EGFR mutations, there is still no general agreement as to their predictive value. To clarify this important issue, the Spanish Lung Cancer Group has opened a Phase III trial comparing erlotinib with chemotherapy in stage IV NSCLC patients with EGFR mutations. This study is open to other European institutions.
Rosell
Rafael
R
Medical Oncology Service, Scientific Director of Oncology Research Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet, s/n 08916 Badalona (Barcelona) Spain. rrosell@ico.scs.es
Taron
Miquel
M
Sanchez
Jose Javier
JJ
Paz-Ares
Luis
L
D001999:Bronchoscopy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D014463:Ultrasonography
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors