title: Updated cost-effectiveness analysis of trastuzumab for early breast cancer: a UK perspective considering duration of benefit, long-term toxicity and pattern of recurrence.
abstract: BACKGROUND
  Trastuzumab has significantly improved survival outcomes for women with Human Epidermal growth factor Receptor 2 (HER2)-positive early breast cancer. Trastuzumab was established as a cost-effective adjuvant treatment in 2006. We present an updated cost-effectiveness analysis from the UK perspective, which explores assumptions about the duration of benefit from treatment, pattern of metastatic recurrence and long-term cardiac toxicity.
  
  
  OBJECTIVE
  The objective of this study was to calculate, from the UK NHS perspective, expected costs (year 2008 values) and benefits over the lifetime of an average cohort of women with HER2-positive early breast cancer treated with or without 1 year of adjuvant trastuzumab sequentially after chemotherapy.
  
  
  METHODS
  A cost-utility analysis was performed using a discrete-state time-dependent semi-Markov model. Probabilistic sensitivity analysis was used to characterize uncertainty around expected outcomes. Value-of-information (VOI) analysis was used to identify areas of priority for further research.
  
  
  RESULTS
  The cost-effectiveness estimates were highly sensitive to the estimated duration of treatment benefit. Trastuzumab remained a cost-effective treatment strategy at a willingness-to-pay threshold of £30,000 per QALY provided the duration of benefit was more than 3.6 years from treatment initiation, assuming the hazard ratio for disease-free survival was 0.63. An increasing proportion of brain metastases with trastuzumab produced a small change towards worse cost effectiveness. Long-term cardiac toxicity needed to rise to high levels to affect overall life expectancy and cost effectiveness. VOI analysis placed highest value on research into the duration of treatment benefit. The relationships between progression-free survival and overall survival and the costs of cancer recurrence were also important.
  
  
  CONCLUSIONS
  The cost effectiveness of adjuvant trastuzumab remains uncertain and dependent on assumptions regarding its clinical effect. Uncertainty around cost effectiveness could be reduced by further research into the duration of treatment effect, particularly in subgroups where this may be shorter. Long-term follow-up is warranted and methods to accurately measure duration of treatment effect and late toxicities should be developed for future adjuvant drug studies.
authors.affiliation: Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK. p.s.hall@leeds.ac.uk
authors.forename: Peter S
authors.initials: PS
authors.lastname: Hall
authors.forename: Claire
authors.initials: C
authors.lastname: Hulme
authors.forename: Christopher
authors.initials: C
authors.lastname: McCabe
authors.forename: Yemi
authors.initials: Y
authors.lastname: Oluboyede
authors.forename: Jeff
authors.initials: J
authors.lastname: Round
authors.forename: David A
authors.initials: DA
authors.lastname: Cameron
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D003362:Cost-Benefit Analysis; D018572:Disease-Free Survival; D005260:Female; D017048:Health Care Costs / Q000592:standards / Q000639:trends; D006801:Humans; D008390:Markov Chains; D018803:Models, Economic; D009364:Neoplasm Recurrence, Local / Q000191:economics* / Q000401:mortality; D013997:Time Factors; D000068878:Trastuzumab; D006113:United Kingdom
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab