Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma.
BACKGROUND
Somatic mutations in EGFR (exons 19 and 21) and KRAS (exon 2) are found in lung adenocarcinomas and have potential prognostic value in patients with advanced disease. These mutations also have therapeutic significance, as they predict for sensitivity and resistance, respectively, to EGFR tyrosine kinase inhibitor therapy. Whether EGFR and KRAS mutations also have an impact on survival in patients who undergo lung resection for curative intent in the absence of targeted therapy has not been established.


METHODS
We analyzed the clinical characteristics and outcomes data for 296 patients who underwent resection at our institution for stage I-III lung adenocarcinoma. Tumors were assessed for both EGFR and KRAS mutations by established methods.


RESULTS
EGFR and KRAS mutations were found in tumors from 40 (14%) and 50 (17%) patients, respectively. Patients with EGFR mutant tumors were more likely to be never smokers (48%), present with stage I disease (88%), and had a 90% (95% confidence interval [CI] 70-97%) 3-year overall survival, whereas patients with KRAS mutant tumors were more likely to be former/current smokers (92%), present with locally advanced disease (40%), and had a 66% (95% CI 48-79%) 3-year overall survival.


CONCLUSIONS
EGFR and KRAS mutations define distinct molecular subsets of resected lung adenocarcinoma. Because EGFR and KRAS mutations also predict whether tumors are sensitive or resistant, respectively, to EGFR tyrosine kinase inhibitors, they can readily be used in clinical trials to help guide the administration of specific types of adjuvant therapy.
Marks
Jenifer L
JL
Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Broderick
Stephen
S
Zhou
Qin
Q
Chitale
Dhananjay
D
Li
Allan R
AR
Zakowski
Maureen F
MF
Kris
Mark G
MG
Rusch
Valerie W
VW
Azzoli
Christopher G
CG
Seshan
Venkatraman E
VE
Ladanyi
Marc
M
Pao
William
W
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016019:Survival Analysis
D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors