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

7519 Background: 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 BR.19 trial exploring the role of adjuvant gefitinib in resected early stage NSCLC (stage IB 49%, II 38%, III 13%) did not show significant progression-free survival (PFS) or overall survival (OS) improvement in all patients. The efficacy of gefitinib following adjuvant chemotherapy in patients with EGFR mutation is unknown. Methods: In this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations (either the exon 19 deletion or L858R point mutation) were randomly assigned to receive pemetrexed (500mg/m2) and carboplatin (AUC=5), administered every 21 days for 4 cycles, followed with (n=30) or without (n=30) gefitinib (250mg per day) for 6 months. The primary end point was PFS. The second end point was OS. Results: From August 2008 toSeptember 2011, 60 patients (35 males and 25 females) were included in our center. Of the 60 patients (56 adenocarcinomas, 2 squamous cell carcinomas, 2 adenosquamous carcinomas), 20 patients (33.3%) had exon 19 deletion mutation, 40 (66.7%) patients had exon 21 L858R point mutation. The most common adverse event was rash (43.3%, 13 of 30) in the pemetrexed and carboplatin (PC)-gefitinib group and the addition of gefitinib to chemotherapy was well tolerated. The PFS was significantly longer among those who received PC-gefitinib than among those who received PC alone (median,39.8 months vs 27.0 months; hazard ratio [HR],0.369; 95% confidence interval [CI], 0.161-0.847; P=0.014). There was no significant difference in OS between the two group(median,41.6 months vs 32.6 months,P=0.066). The rates of 2-year PFS and OS were 78.9% and 92.4% in PC-gefitinib group, and 54.2% and 77.4% in PC alone group, respectively. Conclusions: The addition of gefitinib to pemetrexed and carboplatin adjuvant therapy showed significant improvement in PFS for patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations.