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 [500mg/m 2 ]+cisplatin [75mg/m 2 ] q3 weeks, followed by maintenance with either gefitinib [250mg/d] (PC/G) or pemetrexed [500mg/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 (6.83months; 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.