title: 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.
abstract: BACKGROUND
  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-naïve patients with stage IIIB/IV NSCLC, performance status ≤1 and unknown EGFR mutation status were randomized 1:1 to receive 4 cycles of pemetrexed [500 mg/m(2)]+cisplatin [75 mg/m(2)] q3 weeks, followed by maintenance with either gefitinib [250 mg/d] (PC/G) or pemetrexed [500 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.
authors.affiliation: Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. silk.ahn@samsung.com
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.forename: Jin-Hyoung
authors.initials: JH
authors.lastname: Kang
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Xiu
authors.forename: Yuh-Min
authors.initials: YM
authors.lastname: Chen
authors.forename: Julie Michelle
authors.initials: JM
authors.lastname: Blair
authors.forename: Guangbin
authors.initials: G
authors.lastname: Peng
authors.forename: Carlos
authors.initials: C
authors.lastname: Linn
authors.forename: Mauro
authors.initials: M
authors.lastname: Orlando
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D000077156:Gefitinib; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011799:Quinazolines / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D011799:Quinazolines; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin; D000077156:Gefitinib