Multicentre prospective phase II trial of gefitinib for advanced non-small cell lung cancer with epidermal growth factor receptor mutations: results of the West Japan Thoracic Oncology Group trial (WJTOG0403)

• Published in: British journal of cancer Vol. 98; no. 5; pp. 907 - 914
• Main Authors: Tamura, K, Okamoto, I, Kashii, T, Negoro, S, Hirashima, T, Kudoh, S, Ichinose, Y, Ebi, N, Shibata, K, Nishimura, T, Katakami, N, Sawa, T, Shimizu, E, Fukuoka, J, Satoh, T, Fukuoka, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.03.2008; Nature Publishing Group
• Subjects: Adenocarcinoma, Bronchiolo-Alveolar - drug therapy; Adenocarcinoma, Bronchiolo-Alveolar - genetics; Aged; Aged, 80 and over; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Clinical Study; Disease Progression; Drug Resistance; Epidemiology; Female; Gene Amplification; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Medical sciences; Middle Aged; Molecular Medicine; Mutation; Oncology; Pneumology; Prospective Studies; Quinazolines - adverse effects; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - genetics; Tumors; Tumors of the respiratory system and mediastinum; Asia; Japan; mutation; gefitinib; multicentre prospective phase II; epidermal growth factor receptor; non-small cell lung cancer (NSCLC); central laboratory; Antineoplastic agent; Quinazoline derivatives; Lung cancer; Laboratory; non-small cell lung carcinoma; Epidermal growth factor receptor; Prospective; Cancerology; Phase II trial; Bronchus disease; Clinical trial; Genetics; Advanced stage; Gefitinib; Protein-tyrosine kinase; Lung disease; Enzyme; Tyrosine kinase inhibitor; Respiratory disease; Transferases; Enzyme inhibitor; Malignant tumor; Growth factor receptor; Mutation; Cancer; epidermal growth factor receptor (EGFR) mutation
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604249

The purpose of this study was to evaluate the efficacy of gefitinib and the feasibility of screening for epidermal growth factor receptor ( EGFR ) mutations among select patients with advanced non-small cell lung cancer (NSCLC). Stage IIIB/IV NSCLC, chemotherapy-naive patients or patients with recurrences after up to two prior chemotherapy regimens were eligible. Direct sequencing using DNA from tumour specimens was performed by a central laboratory to detect EGFR mutations. Patients harbouring EGFR mutations received gefitinib. The primary study objective was response; the secondary objectives were toxicity, overall survival (OS), progression-free survival (PFS), 1-year survival (1Y-S) and the disease control rate (DCR). Between March 2005 and January 2006, 118 patients were recruited from 15 institutions and were screened for EGFR mutations, which were detected in 32 patients – 28 of whom were enrolled in the present study. The overall response rate was 75%, the DCR was 96% and the median PFS was 11.5 months. The median OS has not yet been reached, and the 1Y-S was 79%. Thus, gefitinib chemotherapy in patients with advanced NSCLC harbouring EGFR mutations was highly effective. This trial documents the feasibility of performing a multicentre phase II study using a central typing laboratory, demonstrating the benefit to patients of selecting gefitinib treatment based on their EGFR mutation status.