Vinorelbine plus cisplatin after completely resected stage II-III non-small cell lung cancer (NSCLC) is a standard therapy. Stage IV non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFR) is quite sensitive to tyrosine kinase inhibitors (TKIs). Three randomized trials demonstrated that gefitinib is superior to platinum based chemotherapy in progression free survival. Retrospective analysis of adjuvant TKIs therapy for patient with resected lung cancer harboring EGFR mutation showed favorable trend toward improvement in disease free survival (DFS) and overall survival (OS). (J Thorac Oncol. 2011;6: 569–575) BR19 comparing adjuvant gefitinib versus placebo for completely resected NSCLC without any selection of biomarker was closed early and did not show any benefit of adjuvant gefitinib, even in the EGFR mutation positive cohort. The randomized trial in adjuvant therapy with erlotinib versus placebo for patients with overexpression of EGFR protein has complete enrolment already. We conduct the first randomized phase III trial comparing adjuvant gefitinib with chemotherapy in patients with completely resected stage II-III NSCLC harboring EGFR mutations.Methods
Patients who have undergone complete resection and have EGFR mutation, deletions in exon 19, or L858R point mutation at exon 21 and without T790M mutation are randomly assigned gefitinib 250mg a day for 2 years or vinorelbine 25mg/m2 days 1 and 8, plus cisplatin 80mg/m2 day 1, every 3 weeks for 4 courses. The primary end point is DFS and secondary end points are OS and safety. On the basis of previous studies, we assume the hazard ratio of DFS is 0.65. To demonstrate this improvement in DFS, 230 patients in total would be needed during 3-year accrual period.Status Now
This trial has begun from September 12 among 22 institutes in Japan. Until now (March 31. 2012), 20 cases have been enrolled.