title: Randomized phase II study of gefitinib compared with placebo in chemotherapy-naive patients with advanced non-small-cell lung cancer and poor performance status.
abstract: OBJECTIVE
  To compare gefitinib with placebo in chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status.
  
  
  METHODS
  NSCLC patients (chemotherapy naïve, WHO performance status 2 or 3; unfit for chemotherapy; stage IIIB/IV) were randomly assigned to gefitinib (250 mg/d) plus best supportive care (BSC; n = 100) or placebo plus BSC (n = 101). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and safety. Correlation of gefitinib efficacy with EGFR gene copy number (fluorescent in situ hybridization [FISH]) was explored.
  
  
  RESULTS
  Hazard ratios (HRs; gefitinib:placebo) were 0.82 (95% CI, 0.60 to 1.12; P = .217) for PFS and 0.84 (95% CI, 0.62 to 1.15; P = .272) for OS. As expected for this patient population, OS for both arms was poor, at about 3 months. ORRs were 6.0% (gefitinib) and 1.0% (placebo). QOL and PSI rates were 21.1% and 28.3% (gefitinib) and 20.0% and 28.3% (placebo), respectively. In EGFR FISH-positive patients (n = 32), HRs were 0.29 (95% CI, 0.11 to 0.73) for PFS and 0.44 (95% CI, 0.17 to 1.12) for OS. No unexpected adverse events occurred.
  
  
  CONCLUSIONS
  There was no statistically significant difference in PFS, OS, and ORRs after treatment with gefitinib or placebo, in the overall population; improvements in QOL and symptoms were similar in both groups. Tolerability profile of gefitinib was consistent with previous studies. PFS was statistically significantly improved for gefitinib-treated patients with EGFR FISH-positive tumors.
authors.affiliation: Division of Medical Oncology, The Ottawa Hospital Cancer Centre, 501 Smyth Rd, Ottawa, Ontario K1H 8L6, Canada. ggoss@ottawahospital.on.ca
authors.forename: Glenwood
authors.initials: G
authors.lastname: Goss
authors.forename: David
authors.initials: D
authors.lastname: Ferry
authors.forename: Rafal
authors.initials: R
authors.lastname: Wierzbicki
authors.forename: Scott A
authors.initials: SA
authors.lastname: Laurie
authors.forename: Joyce
authors.initials: J
authors.lastname: Thompson
authors.forename: Bonne
authors.initials: B
authors.lastname: Biesma
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: Emma
authors.initials: E
authors.lastname: Duffield
authors.forename: Ozlem U
authors.initials: OU
authors.lastname: Ataman
authors.forename: Marc
authors.initials: M
authors.lastname: Zarenda
authors.forename: Alison A
authors.initials: AA
authors.lastname: Armour
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib