Screening for epidermal growth factor receptor mutations in lung cancer.
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.
Rosell
Rafael
R
Catalan Institute of Oncology and Autonomous University of Barcelona, Hospital Germans Trias i Pujol, Barcelona, Spain.
Moran
Teresa
T
Queralt
Cristina
C
Porta
Rut
R
Cardenal
Felipe
F
Camps
Carlos
C
Majem
Margarita
M
Lopez-Vivanco
Guillermo
G
Isla
Dolores
D
Provencio
Mariano
M
Insa
Amelia
A
Massuti
Bartomeu
B
Gonzalez-Larriba
Jose Luis
JL
Paz-Ares
Luis
L
Bover
Isabel
I
Garcia-Campelo
Rosario
R
Moreno
Miguel Angel
MA
Catot
Silvia
S
Rolfo
Christian
C
Reguart
Noemi
N
Palmero
Ramon
R
Sánchez
José Miguel
JM
Bastus
Roman
R
Mayo
Clara
C
Bertran-Alamillo
Jordi
J
Molina
Miguel Angel
MA
Sanchez
Jose Javier
JJ
Taron
Miquel
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D017678:Sex Distribution; D016019:Survival Analysis; D055815:Young Adult
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors