Randomized phase II trial of first-line treatment with pemetrexed-cisplatin, followed sequentially by gefitinib or pemetrexed, in East Asian, never-smoker patients with advanced non-small cell lung cancer

Introduction: Treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors or chemotherapy have shown improved survival outcomes in East Asian, never-smoker patients with non-small cell lung cancer (NSCLC). However, treatment sequence has not been optimized in patients with unknown EGFR mutation status. This trial compared first-line chemotherapy with pemetrexed (P)-cisplatin (C), followed by either gefitinib (G) or P maintenance. Methods: East Asian, never-smoker, chemo-naive patients with stage IIIB/IV NSCLC, performance status <= 1 and unknown EGFR mutation status were randomized 1:1 to receive 4 cycles of pemetrexed 1500 mg/m(2)] + cisplatin 175 mg/m(2)] q3 weeks, followed by maintenance with either gefitinib [250 mg/d] (PC/G) or pemetrexed 1500 mg/m(2)] q3 weeks and <= 2 optional cycles of cisplatin (PC/P). The primary endpoint, progression-free survival (PFS), was calculated from randomization date. Results: Between Feb and Nov 2007, 70 patients from China, Korea, and Taiwan were randomized and treated, among whom 59 patients (84.3%) had non-squamous NSCLC. Forty-nine patients (70.0%) completed the full sequential treatment (n=25 G; n=24 P). Median PFS was numerically longer for patients on PC/G (9.95 months) than those on PC/P (6.83 months; hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.27, 1.04). In contrast, median overall survival was numerically higher for patients on PC/P (HR=2.15,95% CI=0.83, 5.60), though there was a high censoring rate. Response rate was similar in both arms. Treatment arms were similar for grade 3/4/5 toxicities. Conclusions: East Asian never-smoker patients with advanced NSCLC and unknown EGFR mutation status had improved PFS following treatment with first-line PC and sequential G. Irrespective of subsequent maintenance treatment, induction PC was safe and efficacious, leading to prolonged OS in the Asian patient population. (C) 2012 Elsevier Ireland Ltd. All rights reserved.