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PharmacoEconomics

, Volume 34, Issue 7, pp 673–680 | Cite as

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

  • Hazel Squires
  • Matt Stevenson
  • Emma Simpson
  • Rebecca Harvey
  • John Stevens
Review Article

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.

Keywords

Trastuzumab Capecitabine Lapatinib Evidence Review Group Appraisal Committee 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

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.

Author contributions

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.

References

  1. 1.
    National Institute for Health and Care Excellence. NICE technology appraisal guidance. 2009. Available at: https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nice-technology-appraisal-guidance. Accessed Dec 2015.
  2. 2.
    National Institute for Health and Care Excellence. Trastuzumab emtansine for treating HER2-positive, unresectable locally advanced or metastatic breast cancer after treatment with trastuzumab and a taxane. 2014. Available at: https://www.nice.org.uk/guidance/ta371/. Accessed Jan 2014.
  3. 3.
    European Medicines Agency. 2014. http://www.ema.europa.eu/ema/. Accessed Feb 2014.
  4. 4.
    National Institute for Health and Care Excellence. Breast cancer (HER2 positive, unresectable)—trastuzumab emtansine (after trastuzumab and taxane) (ID603). Manufacturer submission. 2014. Available at: https://www.nice.org.uk/guidance/ta371/history. Accessed Dec 2013.
  5. 5.
    National Institute for Health and Care Excellence. Advanced breast cancer: diagnosis and treatment. NICE guidelines (CG81). 2009. Available at: https://www.nice.org.uk/guidance/cg81. Accessed Jan 2014.
  6. 6.
    Welslau M, et al. Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer. Cancer. 2014;120(5):642–51.CrossRefPubMedGoogle Scholar
  7. 7.
    Wildiers H, Kim S-B, Gonzalez-Martin A, et al. TDM1 for HER2-positive MBC: primary results from TH3RESA, a phase 3 study of T-DM1 vs treatment of physician’s choice (oral presentation). Presented at the European Society for Medical Oncology Congress; 27 Sep–1 Oct 2013: Amsterdam.Google Scholar
  8. 8.
    Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer [published erratum appears in N Engl J Med. 2013;368(25):2442]. N Engl J Med. 2012;367(19):1783–91.CrossRefPubMedGoogle Scholar
  9. 9.
    von MG, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, et al. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer. 2011;47(15):2273–81.Google Scholar
  10. 10.
    Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112(3):533–43.CrossRefPubMedGoogle Scholar
  11. 11.
    Martin M, Bonneterre J, Geyer CE Jr, et al. S5–7: a phase 2, randomized, open-label, study of neratinib (HKI-272) vs lapatinib plus capecitabine for 2nd/3rd-line treatment of HER2+ locally advanced or metastatic breast cancer [abstract no. S5–7]. Cancer Res. 2011;71(24 Suppl).Google Scholar
  12. 12.
    Pivot X, Semiglazov V, Zurawski B, et al. CEREBEL (EGF111438): an open-label randomized phase III study comparing the incidence of CNS metastases in patients with HER2+ metastatic breast cancer, treated with lapatinib plus capecitabine versus trastuzumab plus capecitabine. Presented at the European Society of Medical Oncology Congress; 28 Sep–2 Oct 2012: Vienna.Google Scholar
  13. 13.
    Dieras V, et al. Trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2-positive metastatic breast cancer: pooled safety analysis [abstract no. P5-18-06]. San Antonio Breast Cancer Symposium; 4–8 Dec 2012: San Antonio (TX).Google Scholar
  14. 14.
    National Institute for Health and Clinical Excellence. NICE technology appraisal guidance. 2013. Available at: https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nice-technology-appraisal-guidance. Accessed Dec 2015.
  15. 15.
    Latimer N. NICE Decision Support Unit technical support document 14. Survival analysis for economic evaluations alongside clinical trials: extrapolation with patient-level data. Report by the Decision Support Unit (last updated March 2013). Available at: http://www.nicedsu.org.uk/Survival-analysis-TSD%282892878%29.htm. Accessed Jan 2014.
  16. 16.
    Lloyd A, Nafees B, Narewska J, Dewilde S, Watkins J. Health state utilities for metastatic breast cancer. Br J Cancer. 2006;95(6):683–90.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    British Medical Association, Royal Pharmaceutical Society of Great Britain. British national formulary no. 65. London: British Medical Association, Royal Pharmaceutical Society of Great Britain; 2011.Google Scholar
  18. 18.
    Department of Health. NHS reference costs. 2013. Available at: https://www.gov.uk/government/publications/nhs-reference-costs-2012-to-2013. Accessed Feb 2014.
  19. 19.
    Curtis L. Unit costs of health and social care 2012. University of Kent, Personal Social Services Research Unit. Available at: http://www.pssru.ac.uk/project-pages/unit-costs/2012/. Accessed Jan 2014.
  20. 20.
    Peasgood T, Ward SE, Brazier J. Health-state utility values in breast cancer. Expert Rev Pharmacoecon Outcomes Res. 2010;10(5):553–66.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Hazel Squires
    • 1
  • Matt Stevenson
    • 1
  • Emma Simpson
    • 1
  • Rebecca Harvey
    • 1
  • John Stevens
    • 1
  1. 1.University of SheffieldSheffieldUK

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