title: Cost-Effectiveness Analysis of Different Sequences of the Use of Epidermal Growth Factor Receptor Inhibitors for Wild-Type KRAS Unresectable Metastatic Colorectal Cancer.
abstract: Patients with unresectable wild-type KRAS metastatic colorectal cancer benefit from fluoropyrimidines (FP), oxaliplatin (O), irinotecan (I), bevacizumab (Bev), and epithelial growth factor receptor inhibitors (EGFRI). The most cost-effective regimen remains unclear.
  
  
  
  A Markov model was constructed to examine the costs and outcomes of three treatment strategies: strategy A (reference strategy): EGFRI monotherapy in third line ([3L]; ie, first-line [1L]: Bev + FOLFIRI [FP + I] or FOLFOX [FP + O]; second line [2L]: FOLFIRI/FOLFOX; 3L: EGFRI); strategy B: EGFRI and I in 3L (ie, 1L: Bev + FOLFIRI/FOLFOX; 2L: FOLFIRI/FOLFOX; 3L: EGFRI + I); and strategy C: EGFRI in 1L (ie, 1L: EGFRI + FOLFIRI/FOLFOX; 2L: Bev + FOLFIRI/FOLFOX; 3L: best supportive care). Efficacy data of the treatments were obtained from the literature. Health system resource use information was derived from chart review and the literature. Using Euro-QOL 5 Dimensions, utilities were obtained by surveying medical oncologists and costs from the Ontario Ministry of Health and the literature. The perspective of the Canadian public health care system was used over a 5-year time horizon with a 5% discount in 2012 Canadian dollars.
  
  
  
  All three strategies had similar efficacy, but strategy C was most expensive. The incremental cost-effectiveness ratios (ICERs) for strategies B and C compared with A were 119,623 and 3,176,591, respectively. The model was primarily driven by the acquisition cost of the drugs. Strategy B was most cost effective when the willingness-to-pay threshold was > $130,000 per quality-adjusted life-year. Sensitivity analysis showed that strategy C would be cost-effective only when the progression-free survival of EGFRI is better than Bev in 1L with hazard ratio < 0.23 at willingness-to-pay of $150,000 per quality-adjusted life-year.
  
  
  
  First-line use of EGFRI in metastatic colorectal cancer is not cost effective at its current pricing relative to Bev.
authors.affiliation: University Hospital 12 de Octubre, Madrid, Spain; Odette Cancer Centre; Health Outcomes and PharmacoEconomics Research Centre; and Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Riesco-Martínez
authors.affiliation: University Hospital 12 de Octubre, Madrid, Spain; Odette Cancer Centre; Health Outcomes and PharmacoEconomics Research Centre; and Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Berry
authors.affiliation: University Hospital 12 de Octubre, Madrid, Spain; Odette Cancer Centre; Health Outcomes and PharmacoEconomics Research Centre; and Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yoo-Joung
authors.initials: YJ
authors.lastname: Ko
authors.affiliation: University Hospital 12 de Octubre, Madrid, Spain; Odette Cancer Centre; Health Outcomes and PharmacoEconomics Research Centre; and Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mittmann
authors.affiliation: University Hospital 12 de Octubre, Madrid, Spain; Odette Cancer Centre; Health Outcomes and PharmacoEconomics Research Centre; and Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Angie
authors.initials: A
authors.lastname: Giotis
authors.affiliation: University Hospital 12 de Octubre, Madrid, Spain; Odette Cancer Centre; Health Outcomes and PharmacoEconomics Research Centre; and Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kelly
authors.initials: K
authors.lastname: Lien
authors.affiliation: University Hospital 12 de Octubre, Madrid, Spain; Odette Cancer Centre; Health Outcomes and PharmacoEconomics Research Centre; and Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Toronto, Ontario, Canada.
authors.forename: William W L
authors.initials: WW
authors.lastname: Wong
authors.affiliation: University Hospital 12 de Octubre, Madrid, Spain; Odette Cancer Centre; Health Outcomes and PharmacoEconomics Research Centre; and Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Toronto, Ontario, Canada kelvin.chan@sunnybrook.ca.
authors.forename: Kelvin K W
authors.initials: KK
authors.lastname: Chan
mesh_terms: D000970:Antineoplastic Agents / Q000191:economics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000191:economics / Q000627:therapeutic use; D000068258:Bevacizumab / Q000191:economics / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000191:economics*; D003362:Cost-Benefit Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005472:Fluorouracil / Q000191:economics / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000191:economics / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000191:economics / Q000627:therapeutic use; D016283:Proto-Oncogene Proteins p21(ras); D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin