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Journal of Clinical Oncology, Vol 26, No 16 (June 1), 2008: pp. 2745-2753
© 2008 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2007.15.6695

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Specific EGFR Mutations Predict Treatment Outcome of Stage IIIB/IV Patients With Chemotherapy-Naive Non–Small-Cell Lung Cancer Receiving First-Line Gefitinib Monotherapy

Chih-Hsin Yang, Chong-Jen Yu, Jin-Yuan Shih, Yeun-Chung Chang, Fu-Chang Hu, Meng-Chin Tsai, Kuan-Yu Chen, Zhong-Zhe Lin, Ching-Ju Huang, Chia-Tung Shun, Chin-Lun Huang, James Bean, Ann-Lii Cheng, William Pao, Pan-Chyr Yang

From the Graduate Institute of Clinical Medicine, College of Medicine; Departments of Oncology, Internal Medicine, and Medical Imaging, National Center of Excellence for General Clinical Trial and Research and Department of Pathology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan; and the Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY

Corresponding author: Chih-Hsin Yang, MD, PhD, Department of Oncology, National Taiwan University Hospital. 7, Chung-Shan South Rd, Taipei, Taiwan, 10016; e-mail: chihyang{at}ntu.edu.tw

Purpose: To explore predictive factors for time to treatment failure (TTF) in chemotherapy-naive non–small-cell lung cancer (NSCLC) patients receiving gefitinib treatment.

Patients and Methods: We designed a phase II study to test gefitinib antitumor efficacy in advanced-stage, chemotherapy-naive NSCLC patients. Patients were treated with gefitinib 250 mg/d. Tumor assessments were performed every 2 months. Responding or stable patients were treated until progression or unacceptable toxicity. All scans were reviewed independently. EGFR exons 18-21 sequence, K-ras exon 2 sequence, and MET gene copy numbers were examined in available samples. Clinical or molecular predictors of TTF were examined by multivariate analysis.

Results: One hundred six patients were enrolled. Ninety patients had tumor samples for biomarker tests. Overall response rate was 50.9% (95% CI, 41.4% to 60.4%). Median TTF was 5.5 months, and median overall survival (OS) was 22.4 months. The response rate and median TTF of the patients with exon 19 deletion (n = 20) were 95.0% and 8.9 months, for exon 21 L858R mutation (n = 23) were 73.9% and 9.1 month, and for other types of EGFR mutations (N = 12) were 16.7% and 2.3 months, respectively. In multivariate analysis, the presence of EGFR deletion exon 19 or L858R EGFR mutations in adenocarcinoma patients predicted longer TTF. High copy number of MET seemed to correlate with shorter TTF in patients with gefitinib-sensitive activating EGFR mutations.

Conclusion: In this prospective study, EGFR exon 19 deletion or L858R mutations in adenocarcinoma were the best predictors for longer TTF in stage IIIB/IV chemotherapy-naive NSCLC patients receiving first-line gefitinib monotherapy.

Supported by the Taiwan National Science Council Grant No. NSC95-2314-B-002-227-MY3 and Department of Health Grant No. DOH94-TD-B-111-001, and partially supported by AstraZeneca Taiwan.

Presented in part 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA, and the 12th World Conference on Lung Cancer Research, Seoul, Korea, Septmber 2-6, 2007.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00173875 [ClinicalTrials.gov] .




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