title: Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States.
abstract: Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC).
  
  
  
  We constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression-free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) were captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analyses assessed the uncertainty around key model parameters and their joint impact on the base-case results.
  
  
  
  The combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of $335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. The least clinically effective sequence (1.27 QALYs), but most cost-effective at a total cost of $149,250.19, was trastuzumab/docetaxel as first-line therapy, T-DM1 as second-line therapy, and trastuzumab/lapatinib as third-line therapy.
  
  
  
  Our results suggest that THP as first-line therapy, followed by T-DM1 as second-line therapy, would require at least a 50 % reduction in the total drug acquisition cost for it to be considered a cost-effective strategy.
authors.affiliation: Economic, Social & Administrative Pharmacy, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 200 Dyson Pharmacy Bldg., 1520 Martin Luther King Jr. Blvd., Tallahassee, FL, 32307, USA. diaby_v@yahoo.fr.
authors.forename: Vakaramoko
authors.initials: V
authors.lastname: Diaby
authors.affiliation: Department of Health Behavior and Policy, Virginia Commonwealth University School of Medicine, PO Box 980149, Richmond, VA, 23298, USA.
authors.forename: Georges
authors.initials: G
authors.lastname: Adunlin
authors.affiliation: Economic, Social & Administrative Pharmacy, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 200 Dyson Pharmacy Bldg., 1520 Martin Luther King Jr. Blvd., Tallahassee, FL, 32307, USA.
authors.forename: Askal A
authors.initials: AA
authors.lastname: Ali
authors.affiliation: Winship Cancer Institute at Emory University, 1365 Clifton Road, Atlanta, GA, 30322, USA.
authors.forename: Simon B
authors.initials: SB
authors.lastname: Zeichner
authors.affiliation: Oncoclinicas Group, Avenida Faria Lima 4300, 15 andar, São Paulo, SP, Brazil.
authors.forename: Gilberto
authors.initials: G
authors.lastname: de Lima Lopes
authors.affiliation: Health Economics and Outcomes Research, University of Saint Joseph School of Pharmacy, UConn/Hartford Hospital Evidence-based Practice Center, 229 Trumbull Street, Hartford, CT, 06103, USA.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Kohn
authors.affiliation: Department of Solid Tumor Oncology, Cleveland Clinic, Taussig Cancer Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Montero
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000191:economics / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D003362:Cost-Benefit Analysis; D005260:Female; D017048:Health Care Costs; D006295:Health Resources; D006801:Humans; D008390:Markov Chains; D058990:Molecular Targeted Therapy / Q000191:economics*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010342:Patient Acceptance of Health Care; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D014481:United States / Q000453:epidemiology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: HER2-positive; Markov; T-DM1; Trastuzumab; breast cancer; cost-effectiveness analysis; lapatinib; metastatic breast cancer; pertuzumab; sequential therapy