title: Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial.
abstract: BACKGROUND
  Maintenance treatment of patients with advanced non-small-cell lung cancer (NSCLC) without disease progression after first-line chemotherapy is a subject of ongoing research. The aim of the randomised, double-blind, placebo-controlled, INFORM study was to investigate the efficacy, safety, and tolerability of the EGFR-tyrosine-kinase inhibitor gefitinib in the maintenance setting.
  
  
  METHODS
  Patients were aged 18 years or older, were of east Asian ethnic origin, had a life expectancy of more than 12 weeks, histologically or cytologically confirmed stage IIIb or IV NSCLC, a WHO performance status of 0-2, and had completed four cycles of first-line platinum-based doublet chemotherapy without disease progression or unacceptable toxic effects. Between Sept 28, 2008 and Aug 11, 2009, 296 patients were randomly assigned 1:1 to receive either gefitinib (250 mg per day orally) or placebo (orally) within 3-6 weeks after chemotherapy until progression or unacceptable toxic effects. Randomisation was done via an interactive web response system with computer-generated randomisation codes. Our primary endpoint was progression-free survival assessed in the intention-to-treat population. This completed study is registered with Clinicaltrials.gov, number NCT00770588.
  
  
  RESULTS
  Progression-free survival was significantly longer with gefitinib (n=148) than with placebo (148) (median progression-free survival 4·8 months [95% CI 3·2-8·5] vs 2·6 months [1·6-2·8]; hazard ratio [HR] 0·42, 95% CI 0·33-0·55; p<0·0001). Adverse events occurred more frequently with gefitinib than with placebo; the most common adverse events of any grade were rash (73 [50%] of 147 in the gefitinib group vs 14 [9%] of 148 in the placebo group), diarrhoea (37 [25%] vs 13 [9%]), and alanine aminotransferase increase (31 [21%] vs 12 [8%]). The most commonly reported grade 3 or 4 adverse event was alanine aminotransferase increase (3 [2%] of 147 in the gefitinib group, none of 148 in the placebo group). Ten of 147 (7%) patients given gefitinib and five of 148 (3%) patients given placebo had serious adverse events. Three deaths were thought to be related to treatment with gefitinib: one from interstitial lung disease; one from lung infection; and one from pneumonia.
  
  
  CONCLUSIONS
  Maintenance treatment with gefitinib significantly prolonged progression-free survival compared with placebo in patients from east Asia with advanced NSCLC who achieved disease control after first-line chemotherapy. Clinicians should consider these data when making decisions about maintenance treatment in such patients.
  
  
  BACKGROUND
  AstraZeneca.
authors.affiliation: Cancer Centre, Sun Yat-Sen University, Guangzhou, China. li-zhang@csco.org.cn
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Shenglin
authors.initials: S
authors.lastname: Ma
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Song
authors.forename: Baohui
authors.initials: B
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.forename: Shujun
authors.initials: S
authors.lastname: Yang
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Shun
authors.initials: S
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Shucai
authors.initials: S
authors.lastname: Zhang
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Zhang
authors.forename: Nobuya
authors.initials: N
authors.lastname: Hayashi
authors.forename: Mengzhao
authors.initials: M
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D004311:Double-Blind Method; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib