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 Reguart, Ramon Palmero, José Miguel Sánchez, Roman Bastus, Clara Mayo, Jordi Bertran-Alamillo, Miguel Angel Molina, Jose Javier Sanchez, Miquel Taron, Spanish Lung Cancer Group, M Cuello, C Pallares, P Lianes, J Remon, R Ibeas, P Martinez del Prado, M Angeles Sala, C Santander-Lobera, E Velez de Mendizabal, N Viñolas, J Terrasa, J Valdivia, P Diz, U Jimenez-Berlana, A Velasco-Ortiz de Taranco, E Ales Martinez, R Sanchez-Escribano, A Carrato, C Guillen-Ponce, C Mesia, J Antonio Macias, M Lopez-Brea, J Oramas, I Barneto, P Garrido, M J Mayol, A Lopez, A Artal, A Saenz, S Hernando, M Cobo, R Blanco, R Bernabe, V Guillem, M Angel Muñoz, I Maestu, A Salvatierra, R De Las Peñas, J Alfaro, V Alberola, O Juan, C Martin, J Puertas, E Felip, J F González-González, L Iglesias-Docampo, F J Dorta, M Martinez-Aguillo, E Salgado, R Mesia, E Lastra-Aras, J P Garcia-Muñoz, R Lastra, I Alvarez, J Roig, J Oruezabal, A Poveda, J Lavernia, D Gutierrez, E Filipovich, D Aguiar, D Rodriguez, J Buxo, A F Cardona, P Bes, A Paredes, A M Tortorella, J A Moreno, J Martinez-Garcia, J L Alonso, A Lopez-Martin, M J Echarri-Gonzalez, M Van Kooten, A Guerrero, M Domine, I Diaz, L Heras, R Garcia, I Anton, G Jarchum, R E Bartolucci, M Lomas, A Rubiales, J L Duque, S Escriva de Romani, E Barbeta, J J Reina, J Castro, C Belda, J M Vidal, J M Trigo, C Vadell, J J Zarba, P Esunza, I Garau, A Lopez-Pousa, I De la Gandara, J Widakowich, S Morales, M Martinez, R Luis, M De la Colina, J Calzas, I Garcia-Castro, C Ruiz, P Lopez-Criado, 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 Reguart, Ramon Palmero, José Miguel Sánchez, Roman Bastus, Clara Mayo, Jordi Bertran-Alamillo, Miguel Angel Molina, Jose Javier Sanchez, Miquel Taron, Spanish Lung Cancer Group, M Cuello, C Pallares, P Lianes, J Remon, R Ibeas, P Martinez del Prado, M Angeles Sala, C Santander-Lobera, E Velez de Mendizabal, N Viñolas, J Terrasa, J Valdivia, P Diz, U Jimenez-Berlana, A Velasco-Ortiz de Taranco, E Ales Martinez, R Sanchez-Escribano, A Carrato, C Guillen-Ponce, C Mesia, J Antonio Macias, M Lopez-Brea, J Oramas, I Barneto, P Garrido, M J Mayol, A Lopez, A Artal, A Saenz, S Hernando, M Cobo, R Blanco, R Bernabe, V Guillem, M Angel Muñoz, I Maestu, A Salvatierra, R De Las Peñas, J Alfaro, V Alberola, O Juan, C Martin, J Puertas, E Felip, J F González-González, L Iglesias-Docampo, F J Dorta, M Martinez-Aguillo, E Salgado, R Mesia, E Lastra-Aras, J P Garcia-Muñoz, R Lastra, I Alvarez, J Roig, J Oruezabal, A Poveda, J Lavernia, D Gutierrez, E Filipovich, D Aguiar, D Rodriguez, J Buxo, A F Cardona, P Bes, A Paredes, A M Tortorella, J A Moreno, J Martinez-Garcia, J L Alonso, A Lopez-Martin, M J Echarri-Gonzalez, M Van Kooten, A Guerrero, M Domine, I Diaz, L Heras, R Garcia, I Anton, G Jarchum, R E Bartolucci, M Lomas, A Rubiales, J L Duque, S Escriva de Romani, E Barbeta, J J Reina, J Castro, C Belda, J M Vidal, J M Trigo, C Vadell, J J Zarba, P Esunza, I Garau, A Lopez-Pousa, I De la Gandara, J Widakowich, S Morales, M Martinez, R Luis, M De la Colina, J Calzas, I Garcia-Castro, C Ruiz, P Lopez-Criado
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.
2009 Massachusetts Medical Society
Source: PubMed