Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer Export

@article{citeulike:5539099, 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. 10.1056/NEJMoa0904554}, author = {Rosell, Rafael and Moran, Teresa and Queralt, Cristina and Porta, Rut and Cardenal, Felipe and Camps, Carlos and Majem, Margarita and Lopez-Vivanco, Guillermo and Isla, Dolores and Provencio, Mariano and Insa, Amelia and Massuti, Bartomeu and Gonzalez-Larriba, Jose L. and Paz-Ares, Luis and Bover, Isabel and Garcia-Campelo, Rosario and Moreno, Miguel A. and Catot, Silvia and Rolfo, Christian and Reguart, Noemi and Palmero, Ramon and Sanchez, Jose M. and Bastus, Roman and Mayo, Clara and Bertran-Alamillo, Jordi and Molina, Miguel A. and Sanchez, Jose J. and Taron, Miquel and the Spanish Lung Cancer Group}, citeulike-article-id = {5539099}, citeulike-linkout-0 = {http://dx.doi.org/10.1056/NEJMoa0904554}, citeulike-linkout-1 = {http://content.nejm.org/content/361/10/958.abstract}, citeulike-linkout-2 = {http://content.nejm.org/content/361/10/958.full.pdf}, citeulike-linkout-3 = {http://content.nejm.org/cgi/content/abstract/361/10/958}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/19692684}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=19692684}, day = {3}, doi = {10.1056/NEJMoa0904554}, journal = {N Engl J Med}, keywords = {cancer, medical, policy, screening, twostar}, month = {September}, number = {10}, pages = {958--967}, posted-at = {2009-08-21 18:50:18}, priority = {2}, title = {Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer}, url = {http://dx.doi.org/10.1056/NEJMoa0904554}, volume = {361}, year = {2009} }

TY - JOUR ID - citeulike:5539099 L3 - citeulike-article-id:5539099 N2 - 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. 10.1056/NEJMoa0904554 IS - 10 JF - N Engl J Med EP - 967 TI - Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer VL - 361 SP - 958 KW - cancer KW - medical KW - policy KW - screening KW - twostar AU - Rosell, Rafael AU - Moran, Teresa AU - Queralt, Cristina AU - Porta, Rut AU - Cardenal, Felipe AU - Camps, Carlos AU - Majem, Margarita AU - Lopez-Vivanco, Guillermo AU - Isla, Dolores AU - Provencio, Mariano AU - Insa, Amelia AU - Massuti, Bartomeu AU - Gonzalez-Larriba, Jose AU - Paz-Ares, Luis AU - Bover, Isabel AU - Garcia-Campelo, Rosario AU - Moreno, Miguel AU - Catot, Silvia AU - Rolfo, Christian AU - Reguart, Noemi AU - Palmero, Ramon AU - Sanchez, Jose AU - Bastus, Roman AU - Mayo, Clara AU - Bertran-Alamillo, Jordi AU - Molina, Miguel AU - Sanchez, Jose AU - Taron, Miquel AU - the Spanish Lung Cancer Group PY - 2009/09/03/ UR - http://dx.doi.org/10.1056/NEJMoa0904554 ER -