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

Authors' Affiliations: ¹ Division of Hematology-Oncology, Department of Internal Medicine and ² Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine; ³ Division of Hematology-Oncology, Department of Internal Medicine and ⁴ Department of Pathology, Hanyang University College of Medicine; ⁵ Division of Oncology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine; ⁶ Department of Internal Medicine, Kang Nam St. Mary’s Hospital, The Catholic University; ⁷ Department of Internal Medicine, Yonsei University College of Medicine, Yongdong Severance Hospital; ⁸ Division of Hematology/Oncology, Department of Internal Medicine, Korea University Medical Center, Anam Hospital, Seoul, Korea; ⁹ Research Institute and Hospital, National Cancer Center, Goyang, Korea; ¹⁰ Department of Internal Medicine, Seoul National University, Bundang, Korea; ¹¹ Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea; ¹² Department of Hematology-Oncology, Gachun Medical School Gil Medical Center, Incheon, Korea; ¹³ Department of Internal Medicine, Inje University College of Medicine, Pusan, Korea; ¹⁴ Department of Hematology/Oncology, Ajou University School of Medicine, Suwon, Korea; and ¹⁵ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts

Requests for reprints: Keunchil Park, Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Phone: 82-2-3410-3450; Fax: 82-2-3410-0041; E-mail: kpark{at}smc.samsung.co.kr.

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 ( = 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.