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Published at www.nejm.org August 19, 2009 (10.1056/NEJMoa0904554)

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ABSTRACT

Background Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in patients with advanced non–small-cell lung cancer. We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment.

Methods From April 2005 through November 2008, lung cancers from 2105 patients in 129 institutions in Spain were screened for EGFR mutations. The analysis was performed in a central laboratory. Patients with tumors carrying EGFR mutations were eligible for erlotinib treatment.

Results EGFR mutations were found in 350 of 2105 patients (16.6%). Mutations were more frequent in women (69.7%), in patients who had never smoked (66.6%), and in those with adenocarcinomas (80.9%) (P<0.001 for all comparisons). The mutations were deletions in exon 19 (62.2%) and L858R (37.8%). Median progression-free survival and overall survival for 217 patients who received erlotinib were 14 months and 27 months, respectively. The adjusted hazard ratios for the duration of progression-free survival were 2.94 for men (P<0.001); 1.92 for the presence of the L858R mutation, as compared with a deletion in exon 19 (P=0.02); and 1.68 for the presence of the L858R mutation in paired serum DNA, as compared with the absence of the mutation (P=0.02). The most common adverse events were mild rashes and diarrhea; grade 3 cutaneous toxic effects were recorded in 16 patients (7.4%) and grade 3 diarrhea in 8 patients (3.7%).

Conclusions Large-scale screening of patients with lung cancer for EGFR mutations is feasible and can have a role in decisions about treatment.

Source Information

The authors' affiliations and the names of additional investigators are listed in the Appendix.

This article (10.1056/NEJMoa0904554) was published on August 19, 2009, at NEJM.org.

Address reprint requests to Dr. Rosell at Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet, 08916 Badalona, Spain, or at rrosell{at}ico.scs.es.

Full Text of this Article

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