title: Economic analysis: randomized placebo-controlled clinical trial of erlotinib in advanced non-small cell lung cancer.
abstract: BACKGROUND
  The NCIC Clinical Trials Group conducted the BR.21 trial, a randomized placebo-controlled trial of erlotinib (an epidermal growth factor receptor tyrosine kinase inhibitor) in patients with previously treated advanced non-small cell lung cancer. This trial accrued patients between August 14, 2001, and January 31, 2003, and found that overall survival and quality of life were improved in the erlotinib arm than in the placebo arm. However, funding restrictions limit access to erlotinib in many countries. We undertook an economic analysis of erlotinib treatment in this trial and explored different molecular and clinical predictors of outcome to determine the cost-effectiveness of treating various populations with erlotinib.
  
  
  METHODS
  Resource utilization was determined from individual patient data in the BR.21 trial database. The trial recruited 731 patients (488 in the erlotinib arm and 243 in the placebo arm). Costs arising from erlotinib treatment, diagnostic tests, outpatient visits, acute hospitalization, adverse events, lung cancer-related concomitant medications, transfusions, and radiation therapy were captured. The incremental cost-effectiveness ratio was calculated as the ratio of incremental cost (in 2007 Canadian dollars) to incremental effectiveness (life-years gained). In exploratory analyses, we evaluated the benefits of treatment in selected subgroups to determine the impact on the incremental cost-effectiveness ratio.
  
  
  RESULTS
  The incremental cost-effectiveness ratio for erlotinib treatment in the BR.21 trial population was $94,638 per life-year gained (95% confidence interval = $52,359 to $429,148). The major drivers of cost-effectiveness included the magnitude of survival benefit and erlotinib cost. Subgroup analyses revealed that erlotinib may be more cost-effective in never-smokers or patients with high EGFR gene copy number.
  
  
  CONCLUSIONS
  With an incremental cost-effectiveness ratio of $94 638 per life-year gained, erlotinib treatment for patients with previously treated advanced non-small cell lung cancer is marginally cost-effective. The use of molecular predictors of benefit for targeted agents may help identify more or less cost-effective subgroups for treatment.
authors.affiliation: NCIC Clinical Trials Group, Kingston, ON, Canada.
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Bradbury
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
authors.forename: Pierre K
authors.initials: PK
authors.lastname: Isogai
authors.forename: Liting
authors.initials: L
authors.lastname: Zhu
authors.forename: Raymond
authors.initials: R
authors.lastname: Ng
authors.forename: Nicole
authors.initials: N
authors.lastname: Mittmann
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.forename: William K
authors.initials: WK
authors.lastname: Evans
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002170:Canada; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000191:economics / Q000473:pathology; D003362:Cost-Benefit Analysis; D016527:Drug Costs; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007391:International Cooperation; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000191:economics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D047428:Protein Kinase Inhibitors / Q000191:economics / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases