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
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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.
KeywordsTrastuzumab Capecitabine Lapatinib Evidence Review Group Appraisal Committee
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (project number 12/65/01 STA) (see the HTA programme website for further project information—http://www.hta.ac.uk). This summary of the ERG report was compiled after NICE issued guidance. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of NICE or the Department of Health.
The authors wish to thank Professor Rob Coleman (Professor of Oncology) and Lynda Wyld (Consultant and Senior Lecturer) for providing clinical advice and commenting on draft materials during the project. The authors also acknowledge Helen Buckley Woods (Information Specialist) and Gill Rooney (Project Administrator) who contributed to the work but did not meet the criteria for authorship.
Hazel Squires and Matt Stevenson drafted the manuscript, while Emma Simpson, Rebecca Harvey and John Stevens revised the manuscript for important intellectual content. All authors have given their approval for the final version to be published.
Compliance with Ethical Standards
Conflicts of interest
Hazel Squires, Matt Stevenson, Emma Simpson, Rebecca Harvey and John Stevens have no potential conflicts of interest.
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