title: Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System.
abstract: OBJECTIVE
  Trastuzumab emtansine (T-DM1, KADCYLA(®)) is an antibody-drug conjugate comprised of the cytotoxic agent DM1 and trastuzumab (HERCEPTIN(®)). The safety profile of T-DM1 in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane was investigated in the phase III EMILIA trial. The trial demonstrated clinically and statistically meaningful differences in the safety profile between T-DM1 and capecitabine plus lapatinib (CAP + LAP). The objective of this study was to estimate the costs of managing treatment-related grade ≥ 3 adverse events (AEs) that occurred in ≥ 2% of patients and grade 2 AEs that occurred in ≥ 5% of patients taking T-DM1 compared with patients taking CAP + LAP based on the EMILIA trial, from the perspective of Canadian public payers.
  
  
  METHODS
  An Excel-based model was utilized to estimate the relevant costs. Clinical data were obtained from the EMILIA trial. Cost information was obtained from the literature, clinical experts, and standard cost sources. The analysis was conducted from the Canadian public-payer perspective and reported in 2014 Canadian dollars (CAD).
  
  
  RESULTS
  The management of included treatment-related AEs resulted in higher estimated per-patient costs of CAD6901 for CAP + LAP versus CAD3380 for T-DM1, resulting in savings of CAD3521.
  
  
  CONCLUSIONS
  From a Canadian perspective, this analysis demonstrated that utilizing T-DM1 for the management of HER2-positive metastatic breast cancer results in substantial savings to the public health-care system when considering the costs of treatment-related AEs, due to fewer amount of toxicities compared with CAP + LAP. Results of various sensitivity analyses investigating changes in number and costs of AEs confirmed the findings; however, the magnitude of cost savings varied. Further analyses are necessary to determine whether these cost savings would occur in other countries and health-care systems.
authors.affiliation: CHP Pharma Inc, 20 Maimonides Court, Thornhill, ON, L4J 4X8, Canada, cpiwko@chppharma.com.
authors.forename: Charles
authors.initials: C
authors.lastname: Piwko
authors.forename: Catherine
authors.initials: C
authors.lastname: Prady
authors.forename: Simon
authors.initials: S
authors.lastname: Yunger
authors.forename: Erika
authors.initials: E
authors.lastname: Pollex
authors.forename: Aurelie
authors.initials: A
authors.lastname: Moser
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D002170:Canada; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects*; D003695:Delivery of Health Care; D005260:Female; D017048:Health Care Costs; D006801:Humans; D000077341:Lapatinib; D008453:Maytansine / Q000009:adverse effects / Q000031:analogs & derivatives*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000068878:Trastuzumab
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000069287:Capecitabine; D000077341:Lapatinib; D008453:Maytansine; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human