EGFR mutation-based phase II multicenter trial of gefitinib in advanced non-small cell lung cancer (NSCLC) patients (pts): Results of West Japan Thoracic Oncology Group trial (WJTOG0403)

Abstract

7073 Background: Recently several retrospective analyses have reported that somatic activating mutations in the EGFR tyrosine kinase domain underlie responsiveness to gefitinib. In the present study, we have prospectively assessed whether these specific mutations in EGFR gene affect the clinical outcomes of NSCLC pts treated with gefitinib. Method: Pts with a histologically confirmed, recurrent or metastatic NSCLC that harbored EGFR mutations were eligible for the study. Direct sequencing using DNA extracted from paraffin-embedded tumor specimens to detect mutations in EGFR (exons 18, 19 and 21) was performed in a central laboratory. Eligible pts with measurable lesions, ECOG PS of 0–2, adequate organ functions and less than 2 prior chemotherapy regimens were treated with gefitinib 250 mg orally once daily. The primary objective of this study was to determine the objective response rate of single-agent gefitinib in NSCLC pts with EGFR mutations. With the target activity level of 50% and the lowest response rate of interest set at 25%, 23 eligible patients were required with an 80% power to accept the hypothesis and a 5% significance level to reject the hypothesis. Allowing for a 10% loss to follow-up rate, a total of 25 patients with EGFR mutations were planned to enroll. Results: Between March 2005 and December 2005, 104 patients were recruited from fifteen study centers in Japan and screened for the presence of EGFR mutations. EGFR mutations were detected in 28 pts (27%). Twenty-five of the 28 pts have been enrolled onto this study; 12 pts had deletional mutations in exon 19 and 13 pts had missense mutations (L858R) in exon 21. Of the 25 pts with EGFR mutations: adenocarcinoma (24), female (17), never smoker (18), and PS 0–1 (22). Median age was 69 years (range, 54 to 89 years). Previous therapy included surgery in 9 pts (36%), chemotherapy in 7 pts (28%), and radiotherapy in 1 pts (4%). Conclusions: Efficacy and safety data will be mature in March 2006 and will be presented at the ASCO meeting. These are the first prospective studies targeted at NSCLC pts harboring EGFR mutations. No significant financial relationships to disclose.