8042 Background: Pemetrexed or gefitinib is one of the standard second-line treatments for advanced non-squamousNSCLC in East Asia. The CTONG 0806 a multi-center, randomized, controlled, open-label phase II trial was designed to explore the efficacy of pemetrexed versus gefitinib as the second-line treatment in advanced NSCLC patients without EGFR mutation. Methods: The patients with locally advanced or metastatic, non-squamous NSCLC previously treated with platinum-based chemotherapy and no EGFR mutation in exons 18-21 were enrolled. Patients were 1:1 randomized to receive either gefitinib 250 mg per oral every day (G arm) or pemetrexed 500 mg/m2 iv day 1 with vitamin B12 and folic acid supplement every 21 days (P arm) until disease progression, unacceptable toxicity, or discontinuation of treatment due to other reason. The primary endpoint was progression-free survival (PFS). The secondary endpoints were 4-month and 6-month progression-free survival rate, overall survival (OS), objective response rate (...