title: Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial.
abstract: BACKGROUND
  Two phase II trials in patients with previously-treated advanced non-small-cell lung cancer suggested that gefitinib was efficacious and less toxic than was chemotherapy. We compared gefitinib with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer who had been pretreated with platinum-based chemotherapy.
  
  
  METHODS
  We undertook an open-label phase III study with recruitment between March 1, 2004, and Feb 17, 2006, at 149 centres in 24 countries. 1466 patients with pretreated (>/=one platinum-based regimen) advanced non-small-cell lung cancer were randomly assigned with dynamic balancing to receive gefitinib (250 mg per day orally; n=733) or docetaxel (75 mg/m(2) intravenously in 1-h infusion every 3 weeks; n=733). The primary objective was to compare overall survival between the groups with co-primary analyses to assess non-inferiority in the overall per-protocol population and superiority in patients with high epidermal growth factor receptor (EGFR)-gene-copy number in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00076388.
  
  
  RESULTS
  1433 patients were analysed per protocol (723 in gefitinib group and 710 in docetaxel group). Non-inferiority of gefitinib compared with docetaxel was confirmed for overall survival (593 vs 576 events; hazard ratio [HR] 1.020, 96% CI 0.905-1.150, meeting the predefined non-inferiority criterion; median survival 7.6 vs 8.0 months). Superiority of gefitinib in patients with high EGFR-gene-copy number (85 vs 89 patients) was not proven (72 vs 71 events; HR 1.09, 95% CI 0.78-1.51; p=0.62; median survival 8.4 vs 7.5 months). In the gefitinib group, the most common adverse events were rash or acne (360 [49%] vs 73 [10%]) and diarrhoea (255 [35%] vs 177 [25%]); whereas in the docetaxel group, neutropenia (35 [5%] vs 514 [74%]), asthenic disorders (182 [25%] vs 334 [47%]), and alopecia (23 [3%] vs 254 [36%]) were most common.
  
  
  CONCLUSIONS
  INTEREST established non-inferior survival of gefitinib compared with docetaxel, suggesting that gefitinib is a valid treatment for pretreated patients with advanced non-small-cell lung cancer.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Kim
authors.forename: Vera
authors.initials: V
authors.lastname: Hirsh
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Radj
authors.initials: R
authors.lastname: Gervais
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
authors.forename: Long-Yun
authors.initials: LY
authors.lastname: Li
authors.forename: Claire L
authors.initials: CL
authors.lastname: Watkins
authors.forename: Mark V
authors.initials: MV
authors.lastname: Sellers
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Lowe
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Mei-Lin
authors.initials: ML
authors.lastname: Liao
authors.forename: Kell
authors.initials: K
authors.lastname: Osterlind
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.forename: Alison A
authors.initials: AA
authors.lastname: Armour
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D000077143:Docetaxel; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib