Screening for epidermal growth factor receptor mutations in lung cancer

Rafael Rosell, Teresa Moran, Cristina Queralt, Rut Porta, Felipe Cardenal, Carlos Camps, Margarita Majem, Guillermo Lopez-Vivanco, Dolores Isla, Mariano Provencio, Amelia Insa, Bartomeu Massuti, Jose Luis Gonzalez-Larriba, Luis Paz-Ares, Isabel Bover, Rosario Garcia-Campelo, Miguel Angel Moreno, Silvia Catot, Christian Rolfo, Noemi ReguartRamon Palmero, José Miguel Sánchez, Roman Bastus, Clara Mayo, Jordi Bertran-Alamillo, Miguel Angel Molina, Jose Javier Sanchez, Miquel Taron

Research output: Contribution to journalArticleResearchpeer-review

1899 Citations (Scopus)

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 progressionfree 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. Copyright © 2009 Massachusetts Medical Society.
Original languageEnglish
Pages (from-to)958-967
JournalNew England Journal of Medicine
Volume361
Issue number10
DOIs
Publication statusPublished - 3 Sep 2009

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