Pemetrexed-Carboplatin Adjuvant Chemotherapy With or Without Gefitinib in Resected Stage IIIA-N2 Non-Small Cell Lung Cancer Harbouring EGFR Mutations: A Randomized, Phase II Study

Abstract

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations. The efficacy and safety of gefitinib following adjuvant chemotherapy in patients with EGFR mutation are unknown. In this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations (either exon 19 deletion or L858R point mutation) were assigned randomly to receive pemetrexed (500mg/m(2)) and carboplatin (AUC=5), administered every 21days for 4 cycles, followed with or without gefitinib (250mg/day) for 6months. The primary end point was disease-free survival (DFS). From August 2008 to September 2011, 60 patients were included in our center. DFS was significantly longer among those who received pemetrexed and carboplatin (PC)-gefitinib than among those who received PC alone [hazard ratio (HR), 0.37; 95% confidence interval (CI) 0.16-0.85; P=0.014; median, 39.8 vs. 27.0months]. The rates of 2-year DFS were 78.9% in the PC-gefitinib group and 54.2% in the PC alone group. The rates of 2-year overall survival (OS) were 92.4% in the PC-gefitinib group and 77.4% in the PC alone group (HR, 0.37; 95% CI 0.12-1.11, P=0.076). The most common adverse event was rash (43.3%, 13/30) in the PC-gefitinib group and the administration of gefitinib following chemotherapy was well tolerated. The administration of gefitinib following PC adjuvant therapy shows significant improvement in DFS in patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations.