Document Detail


Prognostic and predictive value of epidermal growth factor receptor tyrosine kinase domain mutation status and gene copy number for adjuvant chemotherapy in non-small cell lung cancer.
MedLine Citation:
PMID:  21107284     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Patients with non-small cell lung carcinoma with epidermal growth factor receptor (EGFR) mutations may have a more favorable prognosis and greater response to chemotherapy. The effect of EGFR mutation and gene copy on patients with early-stage non-small cell lung carcinoma receiving adjuvant chemotherapy has not been reported.
PATIENTS AND METHODS: Tumor samples from NCIC Clinical Trials Group JBR.10, an adjuvant trial of vinorelbine/cisplatin adjuvant chemotherapy [ACT] versus observation (OBS), were analyzed for EGFR mutation by multiple sensitive methods and copy number by fluorescent in situ hybridization. Their prognostic and predictive roles were explored in correlation with survival.
RESULTS: Mutation results were available in 221 OBS and 215 ACT and fluorescent in situ hybridization results in 159 OBS and 163 ACT patients. Mutations were identified in 43 (27 OBS and 16 ACT) patients (36 sensitizing exon 19 deletions or L858R mutations). Compared with wild-type, sensitizing mutations were not significantly prognostic in OBS patients (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.38-1.63, p = 0.53). Although the presence of sensitizing mutations resulted in relatively greater benefit in ACT patients (HR: 0.44, 95% CI: 0.11-1.70, p = 0.22) compared with wild-type patients (HR: 0.78, 95% CI: 0.58-1.06, p = 0.12), this quantitative difference was not significant (interaction p = 0.50). Similarly, high EGFR copy was neither significantly prognostic nor predictive, although quantitatively it was associated with greater benefit from ACT.
CONCLUSIONS: Trends toward longer survival and a greater benefit from chemotherapy were observed in patients with exon 19/21 mutations and high EGFR copy, although the differences were not statistically significant. The interpretation of the results was limited by the low EGFR mutation rate in this study of mainly white patients.
Authors:
Ming-Sound Tsao; Akira Sakurada; Keyue Ding; Sarit Aviel-Ronen; Olga Ludkovski; Ni Liu; Aurélie Le Maître; David Gandara; David H Johnson; James R Rigas; Lesley Seymour; Frances A Shepherd
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer     Volume:  6     ISSN:  1556-1380     ISO Abbreviation:  J Thorac Oncol     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-23     Completed Date:  2011-04-28     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101274235     Medline TA:  J Thorac Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  139-47     Citation Subset:  IM    
Affiliation:
Department of Pathology, University Health Network, Princess Margaret Site, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / drug therapy,  genetics,  pathology
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Carcinoma, Non-Small-Cell Lung / drug therapy*,  genetics,  pathology
Carcinoma, Squamous Cell / drug therapy,  genetics,  pathology
Chemotherapy, Adjuvant
Cisplatin / administration & dosage
DNA, Neoplasm / genetics
Female
Gene Dosage*
Humans
Lung Neoplasms / drug therapy*,  genetics,  pathology
Male
Mutation / genetics*
Neoplasm Staging
Polymerase Chain Reaction
Prognosis
Receptor, Epidermal Growth Factor / genetics*
Survival Rate
Vinblastine / administration & dosage,  analogs & derivatives
Grant Support
ID/Acronym/Agency:
U10 CA077202-10/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Neoplasm; 15663-27-1/Cisplatin; 865-21-4/Vinblastine; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; Q6C979R91Y/vinorelbine
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