title: Trastuzumab Emtansine for Treating HER2-Positive, Unresectable, Locally Advanced or Metastatic Breast Cancer After Treatment with Trastuzumab and a Taxane: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.
abstract: The National Institute for Health and Care Excellence (NICE) invited the manufacturer of trastuzumab emtansine (T-DM1) (Kadcyla(®); Roche) to submit evidence of its clinical and cost-effectiveness for treating human epidermal growth factor receptor 2 (HER2)-positive, unresectable, locally advanced or metastatic breast cancer after treatment with trastuzumab and a taxane. The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield were the independent Evidence Review Group (ERG) who produced a critical review of the company's submission to NICE. The ERG also independently searched for relevant evidence and modified the submitted decision analytic model to produce a revised estimate of cost-effectiveness and examine the impact of altering some of the key assumptions. The clinical effectiveness data were taken from two randomised controlled trials that reported a significant advantage in progression-free survival (PFS) for T-DM1 over lapatinib in combination with capecitabine (EMILIA trial), and over the treatment of physician's choice (TH3RESA trial). A network meta-analysis suggested T-DM1 was the best treatment in terms of both overall survival and PFS compared with lapatinib in combination with capecitabine; trastuzumab in combination with capecitabine; and capecitabine monotherapy. Adverse event (AE) data were taken from a pooled analysis of additional trials of T-DM1 as a single agent. The most common grade 3 or greater AEs for T-DM1 were thrombocytopenia and hepatotoxicity. Following the clarification process, the manufacturer reported a deterministic incremental cost-effectiveness ratio (ICER) for T-DM1 compared with lapatinib in combination with capecitabine of £167,236, the latter of which was estimated to have an ICER of £49,798 compared with capecitabine monotherapy. The ERG produced similar values of £166,429 and £50,620 respectively. All other comparators were dominated. During the appraisal, the manufacturer offered an analysis of a patient access scheme (PAS), which suggested that T-DM1 had a 0 % probability of being cost-effective at an ICER of £30,000 per QALY gained. The NICE Appraisal Committee concluded that while the clinical effectiveness of T-DM1 had been proven, it was not likely to represent a cost-effective use of National Health Service resources and therefore its use could not be recommended.
authors.affiliation: University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK. h.squires@sheffield.ac.uk.
authors.forename: Hazel
authors.initials: H
authors.lastname: Squires
authors.affiliation: University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Matt
authors.initials: M
authors.lastname: Stevenson
authors.affiliation: University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Simpson
authors.affiliation: University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Harvey
authors.affiliation: University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: John
authors.initials: J
authors.lastname: Stevens
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000191:economics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000191:economics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000191:economics / Q000473:pathology; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008453:Maytansine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000191:economics; D009362:Neoplasm Metastasis; D019057:Quality-Adjusted Life Years; D011799:Quinazolines / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000077341:Lapatinib; D008453:Maytansine; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human