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

Myung Ju Ann, Byeong Bae Park, Jin Seok Ann, Sang We Kim, Heung Tae Kim, Jong Seog Lee, Jin Hyung Kang, Jae Yong Cho, Hong Suk Song, Se Hoon Park, Chang Hak Sohn, Sang Won Shin, Jin Hyuck Choi, Chang Seok Ki, Chan Keum Park, Alison J. Holmes, Pasi A. Jänne, Keunchil Park

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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(γ = 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.

Original languageEnglish
Pages (from-to)3860-3866
Number of pages7
JournalClinical Cancer Research
Volume14
Issue number12
DOIs
Publication statusPublished - 2008 Jun 15
Externally publishedYes

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erbB-1 Genes
Non-Small Cell Lung Carcinoma
Gene Amplification
Mutation
Epidermal Growth Factor Receptor
Erlotinib Hydrochloride
Survival
Real-Time Polymerase Chain Reaction
Exons
Proteins
Research Design
Multivariate Analysis
Immunohistochemistry
Prospective Studies
Confidence Intervals

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Are there any ethnic differences in molecular predictors of erlotinib efficacy in advanced non-small cell lung cancer? / Ann, Myung Ju; Park, Byeong Bae; Ann, Jin Seok; Kim, Sang We; Kim, Heung Tae; Lee, Jong Seog; Kang, Jin Hyung; Cho, Jae Yong; Song, Hong Suk; Park, Se Hoon; Sohn, Chang Hak; Shin, Sang Won; Choi, Jin Hyuck; Ki, Chang Seok; Park, Chan Keum; Holmes, Alison J.; Jänne, Pasi A.; Park, Keunchil.

In: Clinical Cancer Research, Vol. 14, No. 12, 15.06.2008, p. 3860-3866.

Research output: Contribution to journalArticle

Ann, MJ, Park, BB, Ann, 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 2008, 'Are there any ethnic differences in molecular predictors of erlotinib efficacy in advanced non-small cell lung cancer?', Clinical Cancer Research, vol. 14, no. 12, pp. 3860-3866. https://doi.org/10.1158/1078-0432.CCR-07-4608
Ann, Myung Ju ; Park, Byeong Bae ; Ann, Jin Seok ; Kim, Sang We ; Kim, Heung Tae ; Lee, Jong Seog ; Kang, Jin Hyung ; Cho, Jae Yong ; Song, Hong Suk ; Park, Se Hoon ; Sohn, Chang Hak ; Shin, Sang Won ; Choi, Jin Hyuck ; Ki, Chang Seok ; Park, Chan Keum ; Holmes, Alison J. ; Jänne, Pasi A. ; Park, Keunchil. / Are there any ethnic differences in molecular predictors of erlotinib efficacy in advanced non-small cell lung cancer?. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 12. pp. 3860-3866.
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AU - Ann, Myung Ju

AU - Park, Byeong Bae

AU - Ann, Jin Seok

AU - Kim, Sang We

AU - Kim, Heung Tae

AU - Lee, Jong Seog

AU - Kang, Jin Hyung

AU - Cho, Jae Yong

AU - Song, Hong Suk

AU - Park, Se Hoon

AU - Sohn, Chang Hak

AU - Shin, Sang Won

AU - Choi, Jin Hyuck

AU - Ki, Chang Seok

AU - Park, Chan Keum

AU - Holmes, Alison J.

AU - Jänne, Pasi A.

AU - Park, Keunchil

PY - 2008/6/15

Y1 - 2008/6/15

N2 - 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(γ = 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.

AB - 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(γ = 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.

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