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Are there any ethnic differences in molecular predictors of erlotinib efficacy in advanced non-small cell lung cancer?

Authors
Ahn, MJ; Park, BB; Ahn, JS; Kim, SW; Kim, HT; Lee, JS; Kang, JH; Cho, JY; Song, HS; Park, SH; Sohn, CH; Shin, SW; Choi, JH; Ki, CS; Park, CK; Holmes, AJ; Jänne, PA; Park, K
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 14(12):3860-3866, 2008
Journal Title
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN
1078-0432
Abstract
PURPOSE: This study investigated possible molecular predictors of outcome in Korean patients with advanced non-small cell lung cancer treated with erlotinib.



EXPERIMENTAL DESIGN: One hundred and twenty patients received erlotinib and were followed prospectively. Ninety-two tissue samples were analyzed for epidermal growth factor receptor (EGFR) gene mutations (exons 18, 19, and 21), 88 for EGFR gene amplification by real-time PCR, and 75 for EGFR protein expression by immunohistochemistry.



RESULTS: The overall tumor response rate was 24.2% (complete response, 4; partial response, 25) with 56.7% of disease control rate. With a median follow-up of 23.6 months, the median time to progression (TTP) was 2.7 months and the median overall survival was 12.9 months. EGFR gene mutations were found in 26.1% (24 of 92), EGFR gene amplification in 40.9% (36 of 88), and EGFR protein expression in 72% (54 of 75). There was a strong association between EGFR gene mutations and gene amplification (gamma = 0.241). Patients with EGFR gene mutations or gene amplification showed both better response rate (58.3% versus 16.2%, P < 0.001; 41.7% versus 17.3%, P = 0.012) and TTP (8.6 versus 2.5 months, P = 0.003; 5.8 versus 1.8 months, P < 0.001) and overall survival (not reached versus 10.8 months, P = 0.023; not reached versus 10.1 months, P = 0.033). By multivariate analysis, EGFR gene mutation was the only significant molecular predictor for TTP (hazard ratio, 0.47; 95% confidence interval, 0.25-0.89).



CONCLUSIONS: Our findings indicate that EGFR gene mutation is a more predictive marker for improved TTP than EGFR gene amplification in erlotinib-treated Korean non-small cell lung cancer patients. Prospective studies from diverse ethnic backgrounds are required to determine the exact role of these molecular markers.
MeSH terms
AdultAgedAged, 80 and overAntineoplastic Agents/administration & dosageAntineoplastic Agents/therapeutic useCarcinoma, Non-Small-Cell Lung/diagnosis*Carcinoma, Non-Small-Cell Lung/drug therapy*Carcinoma, Non-Small-Cell Lung/ethnologyCarcinoma, Non-Small-Cell Lung/geneticsDNA Mutational AnalysisDisease ProgressionDisease-Free SurvivalEthnic Groups/genetics*FemaleGenes, erbB-1HumansLung Neoplasms/diagnosis*Lung Neoplasms/drug therapy*Lung Neoplasms/ethnologyLung Neoplasms/geneticsMaleMiddle AgedMutation/physiologyQuinazolines/administration & dosageQuinazolines/therapeutic use*Time FactorsTreatment OutcomeTumor Markers, Biological/genetics*
DOI
10.1158/1078-0432.CCR-07-4608
PMID
18559606
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Hematology-Oncology
AJOU Authors
최, 진혁
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