Are There Any Ethnic Differences in Molecular Predictors of Erlotinib Efficacy in Advanced Non-Small Cell Lung Cancer?

Myung-Ju AhnByeong-Bae ParkJin Seok AhnSang We KimHeung-Tae KimJong Seog LeeJin Hyung KangJae Yong ChoHong Suk SongSe Hoon ParkChang Hak SohnSangWon ShinJin Hyuck ChoiChang-Seok KiChan Keum ParkAlison J. HolmesPasi A. JänneKeunchil Park
Dept. of Internal Medicine (내과학)
Issue Date
Clinical Cancer Research, Vol.14(12) : 3860-3866, 2008
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 EGFRprotein expressionby immunohistochemistry. Results:The overall tumor response ratewas 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 was12.9 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 (c = 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 10.1months, 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 fromdiverse ethnic backgrounds are required to determine the exact role of these molecular markers.
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