title: Cost-effectiveness analysis of neoadjuvant pertuzumab and trastuzumab therapy for locally advanced, inflammatory, or early HER2-positive breast cancer in Canada.
abstract: OBJECTIVE
  The NeoSphere trial demonstrated that the addition of pertuzumab to trastuzumab and docetaxel for the neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early breast cancer (eBC) resulted in a significant improvement in pathological complete response (pCR). Furthermore, the TRYPHAENA trial supported the benefit of neoadjuvant dual anti-HER2 therapy. Survival data from these trials is not yet available; however, other studies have demonstrated a correlation between pCR and improved event-free survival (EFS) and overall survival (OS) in this patient population. This study represents the first Canadian cost-effectiveness analysis of pertuzumab in the neoadjuvant treatment of HER2-positive eBC.
  
  
  METHODS
  A cost-utility analysis (CUA) was conducted using a three health state Markov model ('event-free', 'relapsed', and 'dead'). Two separate analyses were conducted; the first considering total pCR (ypT0/is ypN0) data from NeoSphere, and the second from TRYPHAENA. Published EFS and OS data partitioned for patients achieving/not achieving pCR were used in combination with the percentage achieving pCR in the pertuzumab trials to estimate survival. This CUA included published utility values and direct medical costs including drugs, treatment administration, management of adverse events, supportive care, and subsequent therapy. To address uncertainty, a probabilistic sensitivity analysis (PSA) and alternative scenarios were explored.
  
  
  RESULTS
  Both analyses suggested that the addition of pertuzumab resulted in increased life-years and quality-adjusted life-years (QALYs). The incremental cost per QALY ranged from $25,388 (CAD; NeoSphere analysis) to $46,196 (TRYPHAENA analysis). Sensitivity analyses further support the use of pertuzumab, with cost-effectiveness ratios ranging from $9230-$64,421. At a threshold of $100,000, the addition of pertuzumab was cost-effective in nearly all scenarios (93% NeoSphere; 79% TRYPHAENA).
  
  
  CONCLUSIONS
  Given the improvement in clinical efficacy and a favorable cost per QALY, the addition of pertuzumab in the neoadjuvant setting represents an attractive treatment option for HER2-positive eBC patients.
authors.affiliation: Cornerstone Research Group Inc. , Burlington, ON , Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Attard
authors.forename: A N
authors.initials: AN
authors.lastname: Pepper
authors.forename: S T
authors.initials: ST
authors.lastname: Brown
authors.forename: M F
authors.initials: MF
authors.lastname: Thompson
authors.forename: P-O
authors.initials: PO
authors.lastname: Thuresson
authors.forename: S
authors.initials: S
authors.lastname: Yunger
authors.forename: S
authors.initials: S
authors.lastname: Dent
authors.forename: A H
authors.initials: AH
authors.lastname: Paterson
authors.forename: G A
authors.initials: GA
authors.lastname: Wells
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000191:economics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D002170:Canada; D003362:Cost-Benefit Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008390:Markov Chains; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab / Q000191:economics / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C485206:pertuzumab
keywords: Breast cancer; Cost-effectiveness analysis; Cost-utility analysis; HER2-positive; Neoadjuvant; Pertuzumab; Trastuzumab