Document Detail


Distinct clinical course of EGFR-mutant resected lung cancers: results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib.
MedLine Citation:
PMID:  23154553     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: EGFR and KRAS mutations are mutually exclusive and predict outcomes with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in patients with stage IV lung cancers. The clinical significance of these mutations in patients with resected stage I-III lung cancers is unclear.
METHODS: At our institution, resection specimens from patients with stage I-III lung adenocarcinomas are tested for the presence of EGFR or KRAS mutations during routine pathology analysis such that the results are available before consideration of adjuvant therapy. In a cohort of 1118 patients tested over 8 years, overall survival was analyzed using multivariate analysis to control for potential confounders, including age, sex, stage, and smoking history. The impact of adjuvant erlotinib or gefitinib was examined in an independent data set of patients exclusively with EGFR mutation, in which date of recurrence was recorded.
RESULTS: In the overall population, we identified 227 KRAS (25%) and 222 EGFR (20%) mutations. Patients with EGFR-mutant lung cancers had a lower risk of death compared with those without EGFR mutations, overall survival (OS) HR 0.51 (95% confidence interval [CI]: 0.34-0.76, p < 0.001). Patients with KRAS-mutant lung cancers had similar outcomes compared with individuals with KRAS wild-type tumors, OS HR 1.17 (95% CI: 0.87-1.57, p = 0.30). A separate data set includes only patients with EGFR-mutant lung cancers identified over 10 years (n = 286). In patients with resected lung cancers and EGFR mutation, treatment with adjuvant erlotinib or gefitinib was associated with a lower risk of recurrence or death, disease-free survival HR 0.43 (95% CI: 0.26-0.72, p = 0.001), and a trend toward improved OS.
CONCLUSIONS: Patients with resected stage I-III lung cancers and EGFR mutation have a lower risk of death compared with patients without EGFR mutation. This may be because of treatment with EGFR TKIs. Patients with, and without KRAS mutation have similar OS. These data support reflex testing of resected lung adenocarcinomas for EGFR mutation to provide prognostic information and identify patients for enrollment on prospective clinical trials of adjuvant EGFR TKIs.
Authors:
Sandra P D'Angelo; Yelena Y Janjigian; Nicholas Ahye; Gregory J Riely; Jamie E Chaft; Camelia S Sima; Ronglai Shen; Junting Zheng; Joseph Dycoco; Mark G Kris; Maureen F Zakowski; Marc Ladanyi; Valerie Rusch; Christopher G Azzoli
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer     Volume:  7     ISSN:  1556-1380     ISO Abbreviation:  J Thorac Oncol     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-05-07     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  101274235     Medline TA:  J Thorac Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1815-22     Citation Subset:  IM    
Affiliation:
Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / drug therapy*,  genetics,  mortality,  surgery
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Carcinoma, Non-Small-Cell Lung / drug therapy*,  genetics,  mortality,  surgery
Female
Follow-Up Studies
Humans
Lung Neoplasms / drug therapy*,  genetics,  mortality,  surgery
Male
Middle Aged
Mutation / genetics*
Neoplasm Staging
Prognosis
Proto-Oncogene Proteins / genetics
Quinazolines / administration & dosage
Receptor, Epidermal Growth Factor / genetics*
Retrospective Studies
Survival Rate
Young Adult
ras Proteins / genetics
Chemical
Reg. No./Substance:
0/KRAS protein, human; 0/Proto-Oncogene Proteins; 0/Quinazolines; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 3.6.5.2/ras Proteins; J4T82NDH7E/erlotinib; S65743JHBS/gefitinib

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