title: Prospective cost-effectiveness analysis of cetuximab in metastatic colorectal cancer: evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 trial.
abstract: BACKGROUND
  The National Cancer Institute of Canada Clinical Trials Group CO.17 study showed that patients with advanced colorectal cancer had improved overall survival when cetuximab, an epidermal growth factor receptor-targeting antibody, was given in addition to best supportive care. We conducted a cost-effectiveness analysis using prospectively collected resource utilization and health utility data for patients in the CO.17 study who received cetuximab plus best supportive care (N = 283) or best supportive care alone (N = 274).
  
  
  METHODS
  Direct medical resource utilization data were collected, including medications, physician visits, toxicity management, blood products, emergency department visits, and hospitalizations. Mean survival times for the study arms were calculated for the entire population and for the subset of patients with wild-type KRAS tumors over an 18- to 19-month period. All costs were presented in 2007 Canadian dollars. One-way and probabilistic sensitivity analysis was used to determine the robustness of the results. Cost-effectiveness acceptability curves were determined. The 95% confidence intervals (CIs) for the incremental cost-effectiveness ratios and the incremental cost-utility ratios were estimated by use of a nonparametric bootstrapping method (with 1000 iterations).
  
  
  RESULTS
  For the entire study population, the mean improvement in overall and quality-adjusted survival with cetuximab was 0.12 years and 0.08 quality-adjusted life-years (QALYs), respectively. The incremental cost with cetuximab compared with best supportive care was $23,969. The incremental cost-effectiveness ratio was $199,742 per life-year gained (95% CI = $125,973 to $652,492 per life-year gained) and the incremental cost-utility ratio was $299,613 per QALY gained (95% CI = $187,440 to $898,201 per QALY gained). For patients with wild-type KRAS tumors, the incremental cost with cetuximab was $33,617 and mean gains in overall and quality-adjusted survival were 0.28 years and 0.18 QALYs, respectively. The incremental cost-effectiveness ratio was $120,061 per life-year gained (95% CI = $88,679 to $207,075 per life-year gained) and the incremental cost-utility ratio was $186,761 per QALY gained (95% CI = $130,326 to $334,940 per QALY gained). In a sensitivity analysis, cetuximab cost and patient survival were the only variables that influenced cost-effectiveness.
  
  
  CONCLUSIONS
  The incremental cost-effectiveness ratio of cetuximab over best supportive care alone in unselected advanced colorectal cancer patients is high and sensitive to drug cost. Incremental cost-effectiveness ratios were lower when the analysis was limited to patients with wild-type KRAS tumors.
authors: Health Outcomes and Pharmacoeconomics Research Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. nicole.mittmann@sunnybrook.ca
authors: Nicole
authors: N
authors: Mittmann
authors: Heather-Jane
authors: HJ
authors: Au
authors: Dongsheng
authors: D
authors: Tu
authors: Christopher J
authors: CJ
authors: O'Callaghan
authors: Pierre K
authors: PK
authors: Isogai
authors: Christos S
authors: CS
authors: Karapetis
authors: John R
authors: JR
authors: Zalcberg
authors: William K
authors: WK
authors: Evans
authors: Malcolm J
authors: MJ
authors: Moore
authors: Jehan
authors: J
authors: Siddiqui
authors: Brian
authors: B
authors: Findlay
authors: Bruce
authors: B
authors: Colwell
authors: John
authors: J
authors: Simes
authors: Peter
authors: P
authors: Gibbs
authors: Matthew
authors: M
authors: Links
authors: Niall C
authors: NC
authors: Tebbutt
authors: Derek J
authors: DJ
authors: Jonker
mesh_terms: D000911:Antibodies, Monoclonal / Q000191:economics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000191:economics* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002170:Canada; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000191:economics* / Q000401:mortality; D016001:Confidence Intervals; D003362:Cost-Benefit Analysis; D016527:Drug Costs; D066246:ErbB Receptors / Q000187:drug effects; D017048:Health Care Costs; D006295:Health Resources / Q000191:economics / Q000706:statistics & numerical data; D006801:Humans; D009154:Mutation; D018579:Patient Selection; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D019057:Quality-Adjusted Life Years; D012107:Research Design; D016019:Survival Analysis; D018631:ras Proteins / Q000032:analysis* / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab