title: Cost-effectiveness analysis of second-line tyrosine kinase inhibitor treatment for chronic myelogenous leukemia.
abstract: OBJECTIVE
  A cost-effectiveness analysis was performed for sequential treatments of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors (TKIs) after failure of 1st line imatinib, from a commercial payer perspective in the US.
  
  
  METHODS
  A Markov model was developed to simulate lifetime treatment costs and health outcomes for TKI sequences for treatment of patients resistant or intolerant to 1st-line imatinib. Five health states were included, chronic phase 2nd-line TKI, chronic phase 3rd-line TKI, chronic phase post-TKI, advanced phases, and death. Efficacy (response achievement, loss of response, transformation, death) and safety (adverse events incidence, discontinuation) data are based on clinical trials. Resource utilization, costs, and utilities were based on product labels and publically available data. Uncertainty analyses were conducted for key inputs.
  
  
  RESULTS
  In patients failing imatinib, dasatinib-initiating treatment sequences provide the most survival (ΔLYs = 0.2-2.0), QALYs (ΔQALYs = 0.2-1.9), and accrue highest CML-related costs (ΔCosts = $64,000-$222,000). The average ICER per QALY for dasatinib- vs imatinib-initiating sequences is $100,000 for an imatinib-resistant population. The average ICER per QALY for dasatinib- vs nilotinib-initiating sequences is $170,000 for an imatinib-resistant population, and $160,000 for an imatinib-intolerant population.
  
  
  CONCLUSIONS
  This analysis suggests that dasatinib is associated with increased survival and quality of life compared to high dose imatinib and to a smaller extent with nilotinib, among patients resistant or intolerant to 1st-line imatinib, primarily based on higher cytogenetic response rates observed in clinical studies of dasatinib. Head-to-head studies of sequential use of dasatinib and nilotinib are needed to validate the model findings of improved survival (LYs) with better quality-of-life (QALYs) for patients initiating dasatinib in 2nd-line. However, the model findings (in light of higher cytogenetic response rates with dasatinib) are supported by other studies showing improved quality-of-life for responders, and improved survival for patients achieving cytogenetic response.
authors.affiliation: a a Evidera Inc. , London , UK.
authors.forename: John
authors.initials: J
authors.lastname: Whalen
authors.affiliation: b b Evidera , Lexington , MA , USA.
authors.forename: Ipek
authors.initials: I
authors.lastname: Stillman
authors.affiliation: a a Evidera Inc. , London , UK.
authors.forename: Apoorva
authors.initials: A
authors.lastname: Ambavane
authors.affiliation: c c Bristol-Myers Squibb , Plainsboro , NJ , USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Felber
authors.affiliation: c c Bristol-Myers Squibb , Plainsboro , NJ , USA.
authors.forename: Dinara
authors.initials: D
authors.lastname: Makenbaeva
authors.affiliation: c c Bristol-Myers Squibb , Plainsboro , NJ , USA.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Bolinder
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003362:Cost-Benefit Analysis; D000069439:Dasatinib / Q000191:economics* / Q000627:therapeutic use; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006296:Health Services / Q000191:economics / Q000706:statistics & numerical data; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008390:Markov Chains; D008875:Middle Aged; D017059:Models, Econometric; D047428:Protein Kinase Inhibitors / Q000191:economics* / Q000627:therapeutic use; D011743:Pyrimidines / Q000191:economics* / Q000627:therapeutic use; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D016019:Survival Analysis
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib
keywords: Chronic myelogenous leukemia; Cost-effectiveness analysis; Dasatinib; Economic analysis; TKI