Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Original article

Vol. 149 No. 1920 (2019)

Adjuvant trastuzumab chemotherapy in early breast cancer: meta-analysis of randomised trials and cost-effectiveness analysis

  • Tan Nhut Doan
  • Jan Barendregt
DOI
https://doi.org/10.4414/smw.2019.20082
Cite this as:
Swiss Med Wkly. 2019;149:w20082
Published
19.05.2019

Summary

BACKGROUND

Trastuzumab has a large financial impact on the average cost of breast cancer treatment. This study reassessed the cost-effectiveness of listing the drug on the subsidised Australian Pharmaceutical Benefits Scheme.

METHODS

Using a continuous-time, discrete-event microsimulation model, we examined the effect of 1-year trastuzumab on the total number of disability-adjusted life-years (DALYs) averted among Australian women with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. Target population was women aged 30–100 years and newly diagnosed with the disease in 2003. The model adjusted for tumour size and followed the women up until death or age 100 years. Uncertainty was examined in univariate and probabilistic multivariate sensitivity analyses.

RESULTS

The incremental cost-effectiveness ratio (ICER) was A$132,537 (95% confidence interval 91,172–200,485) per DALY averted. Results were sensitive to restriction of trastuzumab to high-risk (large tumour) and/or high-benefit (young) patients. Suitable combinations of tumour size and age restrictions would improve the cost-effectiveness of trastuzumab. Specifically, restricting trastuzumab to women aged 40 years or younger with tumour sizes 40+ mm reduced the ICER to A$35,290 per DALY averted.

CONCLUSION

Trastuzumab for HER2-positive early breast cancer had a high ICER. It is unclear why the Pharmaceutical Benefits Scheme listing does not use restrictions to improve the cost-effectiveness of the drug.

References

  1. Fabi A, Malaguti P, Vari S, Cognetti F. First-line therapy in HER2 positive metastatic breast cancer: is the mosaic fully completed or are we missing additional pieces? J Exp Clin Cancer Res. 2016;35(1):104. doi:.https://doi.org/10.1186/s13046-016-0380-5
  2. Pharmaceutical Benefits Advisory Committee. Public summary document (trastuzumab). 2006. Available at http://www.health.gov.au/internet/main/publishing.nsf/Content/C876BD009518915CCA2572110018BEC9/$File/Trastuzumab.pdf
  3. Australian Government Department of Health. Pharmaceutical Benefits Scheme. 2011. Available at http://pbs.gov.au/pbs/search?term=trastuzumab&search-type=medicines
  4. Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, et al.; Herceptin Adjuvant (HERA) Trial Study Team. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075):1195–205. doi:.https://doi.org/10.1016/S0140-6736(16)32616-2
  5. Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE, Jr, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014;32(33):3744–52. doi:.https://doi.org/10.1200/JCO.2014.55.5730
  6. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al.; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659–72. doi:.https://doi.org/10.1056/NEJMoa052306
  7. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Jr, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673–84. doi:.https://doi.org/10.1056/NEJMoa052122
  8. Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, et al.; HERA study team. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007;369(9555):29–36. doi:.https://doi.org/10.1016/S0140-6736(07)60028-2
  9. Balduzzi S, Mantarro S, Guarneri V, Tagliabue L, Pistotti V, Moja L, et al. Trastuzumab-containing regimens for metastatic breast cancer. Cochrane Database Syst Rev. 2014;(6):CD006242.
  10. Dedes KJ, Szucs TD, Imesch P, Fedier A, Fehr MK, Fink D. Cost-effectiveness of trastuzumab in the adjuvant treatment of early breast cancer: a model-based analysis of the HERA and FinHer trial. Ann Oncol. 2007;18(9):1493–9. doi:.https://doi.org/10.1093/annonc/mdm185
  11. Kurian AW, Thompson RN, Gaw AF, Arai S, Ortiz R, Garber AM. A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer. J Clin Oncol. 2007;25(6):634–41. doi:.https://doi.org/10.1200/JCO.2006.06.3081
  12. Millar JA, Millward MJ. Cost effectiveness of trastuzumab in the adjuvant treatment of early breast cancer: a lifetime model. Pharmacoeconomics. 2007;25(5):429–42. doi:.https://doi.org/10.2165/00019053-200725050-00006
  13. Hall PS, Hulme C, McCabe C, Oluboyede Y, Round J, Cameron DA. Updated cost-effectiveness analysis of trastuzumab for early breast cancer: a UK perspective considering duration of benefit, long-term toxicity and pattern of recurrence. Pharmacoeconomics. 2011;29(5):415–32. doi:.https://doi.org/10.2165/11588340-000000000-00000
  14. Lidgren M, Jönsson B, Rehnberg C, Willking N, Bergh J. Cost-effectiveness of HER2 testing and 1-year adjuvant trastuzumab therapy for early breast cancer. Ann Oncol. 2007;19(3):487–95. doi:.https://doi.org/10.1093/annonc/mdm488
  15. Luke C, Gill G, Birrell S, Humeniuk V, Borg M, Karapetis C, et al. Treatment and survival from breast cancer: the experience of patients at South Australian teaching hospitals between 1977 and 2003. J Eval Clin Pract. 2007;13(2):212–20. doi:.https://doi.org/10.1111/j.1365-2753.2006.00678.x
  16. Begg S, Vos T, Barker B, Stevenson C, Stanley L, Alan D, et al. The burden of disease and injury in Australia 2003. PHE 82. Canberra: AIHW; 2007.
  17. Muñoz M, Fernández-Aceñero MJ, Martín S, Schneider J. Prognostic significance of molecular classification of breast invasive ductal carcinoma. Arch Gynecol Obstet. 2009;280(1):43–8. doi:.https://doi.org/10.1007/s00404-008-0867-1
  18. Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE, Jr, et al. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011;29(25):3366–73. doi:.https://doi.org/10.1200/JCO.2011.35.0868
  19. Dennis Slamon. BCIRG 006 phase III randomized trial comparing AC→T with AC→TH and with TCH in the adjuvant treatment of HER2-amplified early breast cancer patients: third planned efficacy analysis. 2009. Available at http://www.bcirg.org/NR/rdonlyres/eno7mvfpseiqi5g3pernz37zzeavin4f7o5hos4zwlu76clvwkfluhskusgcmnqvyqk7ksb4gdimpmt6xcmkxppnqce/945_GS5_02_+abst+62+Jan+10.pdf
  20. Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, et al. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol. 2009;27(34):5685–92. doi:.https://doi.org/10.1200/JCO.2008.21.4577
  21. Matthias E, George DS, Douglas GA. Systematic reviews in health care: meta‐analysis in context. BMJ Publishing Group. 2008.
  22. Bria E, Cuppone F, Fornier M, Nisticò C, Carlini P, Milella M, et al. Cardiotoxicity and incidence of brain metastases after adjuvant trastuzumab for early breast cancer: the dark side of the moon? A meta-analysis of the randomized trials. Breast Cancer Res Treat. 2008;109(2):231–9. doi:.https://doi.org/10.1007/s10549-007-9663-z
  23. Caro JJ. Pharmacoeconomic analyses using discrete event simulation. Pharmacoeconomics. 2005;23(4):323–32. doi:.https://doi.org/10.2165/00019053-200523040-00003
  24. Marlies EAS, Marie-Louise EB, Gouke JB, Jan JB, Pieter GNK, Harry PA, et al. Disability weights for diseases in the Netherlands. Rotterdam: Erasmus University Rotterdam. 1997.
  25. Australian Government Department of Health. The Pharmaceutical Benefits Scheme. 2018. Available at http://www.pbs.gov.au/pbs/home
  26. Dunstan DW, Zimmet PZ, Welborn TA, De Courten MP, Cameron AJ, Sicree RA, et al. The rising prevalence of diabetes and impaired glucose tolerance: the Australian Diabetes, Obesity and Lifestyle Study. Diabetes Care. 2002;25(5):829–34. doi:.https://doi.org/10.2337/diacare.25.5.829
  27. Australian Government Department of Health. The Medicare Benefits Schedule. 2018. Available at http://www.mbsonline.gov.au/internet/mbsonline/publishing.nsf/Content/Home
  28. National Breast and Ovarian Cancer Centre. Recommendations for use of Trastuzumab for the treatment of HER2-positive breast cancer. 2011. Available at http://guidelines.nbocc.org.au/guidelines/trastuzumab/
  29. Smith DH, Gravelle H. The practice of discounting in economic evaluations of healthcare interventions. Int J Technol Assess Health Care. 2001;17(2):236–43. doi:.https://doi.org/10.1017/S0266462300105094
  30. Roche. Herceptin (trastuzumab): achieving clinical excellence in the adjuvant treatment of HER-2 positive breast cancer. Roche submission to the National Institute for Health and Clinical Excellence 2006. Available at https://www.nice.org.uk/guidance/ta107/documents/roche2
  31. Garrison LP, Jr, Lubeck D, Lalla D, Paton V, Dueck A, Perez EA. Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer. Cancer. 2007;110(3):489–98. doi:.https://doi.org/10.1002/cncr.22806
  32. Lang HC, Chen HW, Chiou TJ, Chan AL. The real-world cost-effectiveness of adjuvant trastuzumab in HER-2/neu-positive early breast cancer in Taiwan. J Med Econ. 2016;19(10):923–7. doi:.https://doi.org/10.1080/13696998.2016.1185013
  33. Chen W, Jiang Z, Shao Z, Sun Q, Shen K. An economic evaluation of adjuvant trastuzumab therapy in HER2-positive early breast cancer. Value Health. 2009;12(Suppl 3):S82–4. doi:.https://doi.org/10.1111/j.1524-4733.2009.00634.x
  34. Shiroiwa T, Fukuda T, Shimozuma K, Ohashi Y, Tsutani K. The model-based cost-effectiveness analysis of 1-year adjuvant trastuzumab treatment: based on 2-year follow-up HERA trial data. Breast Cancer Res Treat. 2008;109(3):559–66. doi:.https://doi.org/10.1007/s10549-007-9679-4
  35. Aboutorabi A, Hadian M, Ghaderi H, Salehi M, Ghiasipour M. Cost-effectiveness analysis of trastuzumab in the adjuvant treatment for early breast cancer. Glob J Health Sci. 2014;7(1):98–106. doi:.https://doi.org/10.5539/gjhs.v7n1p98
  36. Clarke CS, Hunter RM, Shemilt I, Serra-Sastre V. Multi-arm Cost-Effectiveness Analysis (CEA) comparing different durations of adjuvant trastuzumab in early breast cancer, from the English NHS payer perspective. PLoS One. 2017;12(3):e0172731. doi:.https://doi.org/10.1371/journal.pone.0172731
  37. Buendía JA, Vallejos C, Pichón-Rivière A. An economic evaluation of trastuzumab as adjuvant treatment of early HER2-positive breast cancer patients in Colombia. Biomedica. 2013;33(3):411–7.
  38. Earle CC, Chapman RH, Baker CS, Bell CM, Stone PW, Sandberg EA, et al. Systematic overview of cost-utility assessments in oncology. J Clin Oncol. 2000;18(18):3302–17. doi:.https://doi.org/10.1200/JCO.2000.18.18.3302
  39. Karnon J, Brown J. Selecting a decision model for economic evaluation: a case study and review. Health Care Manage Sci. 1998;1(2):133–40. doi:.https://doi.org/10.1023/A:1019090401655
  40. Neyt M, Huybrechts M, Hulstaert F, Vrijens F, Ramaekers D. Trastuzumab in early stage breast cancer: a cost-effectiveness analysis for Belgium. Health Policy. 2008;87(2):146–59. doi:.https://doi.org/10.1016/j.healthpol.2007.11.003
  41. Ewer MS, Vooletich MT, Durand JB, Woods ML, Davis JR, Valero V, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol. 2005;23(31):7820–6. doi:.https://doi.org/10.1200/JCO.2005.13.300
  42. Perez EA, Suman VJ, Davidson NE, Sledge GW, Kaufman PA, Hudis CA, et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol. 2008;26(8):1231–8. doi:.https://doi.org/10.1200/JCO.2007.13.5467
  43. Telli ML, Hunt SA, Carlson RW, Guardino AE. Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J Clin Oncol. 2007;25(23):3525–33. doi:.https://doi.org/10.1200/JCO.2007.11.0106
  44. Norum J, Olsen JA, Wist EA, Lønning PE. Trastuzumab in adjuvant breast cancer therapy. A model based cost-effectiveness analysis. Acta Oncol. 2007;46(2):153–64. doi:.https://doi.org/10.1080/02841860601096841
  45. Grosse SD, Lollar DJ, Campbell VA, Chamie M. Disability and disability-adjusted life years: not the same. Public Health Rep. 2009;124(2):197–202. doi:.https://doi.org/10.1177/003335490912400206
  46. Fox-Rushby JA. Disability-adjusted life years (DALYs) for decision-making? An overview of the literature. Office of Health Economics. 2002. Available at https://www.ohe.org/publications/disability-adjusted-life-years-dalys-decision-making
  47. Thacker SB, Stroup DF, Carande-Kulis V, Marks JS, Roy K, Gerberding JL. Measuring the public’s health. Public Health Rep. 2006;121(1):14–22. doi:.https://doi.org/10.1177/003335490612100107
  48. Lajoie J. Understanding the measurement of Global Burden of Disease. 2015. Available at https://nccid.ca/publications/understanding-the-measurement-of-global-burden-of-disease/
  49. Brazier J, Ratcliffe J, Salomon J, Tsuchiya A. Measuring and valuing health benefits for economic evaluation. 2016. Oxford: Oxford University Press.
  50. Cairns J. Using cost-effectiveness evidence to inform decisions as to which health services to provide. Health Systems Reform. 2016;2??
  51. Grosse SD. Assessing cost-effectiveness in healthcare: history of the $50,000 per QALY threshold. Expert Rev Pharmacoecon Outcomes Res. 2008;8(2):165–78. doi:.https://doi.org/10.1586/14737167.8.2.165
  52. Elliott R, Payne K. Essentials of economic evaluation in healthcare. 2004. London: Pharmaceutical Press.
  53. Corso PS, Hammitt JK, Graham JD, Dicker RC, Goldie SJ. Assessing preferences for prevention versus treatment using willingness to pay. Med Decis Making. 2002;22(1, Suppl):S92–101. doi:.https://doi.org/10.1177/027298902237713
  54. Franic DM, Pathak DS, Gafni A. Quality-adjusted life years was a poor predictor of women’s willingness to pay in acute and chronic conditions: results of a survey. J Clin Epidemiol. 2005;58(3):291–303. doi:.https://doi.org/10.1016/j.jclinepi.2004.10.005
  55. Australian Institute of Health and Welfare. Breast cancer in Australia: an overview. Canberra; AIHW: 2009.
  56. Raftery JP. Paying for costly pharmaceuticals: regulation of new drugs in Australia, England and New Zealand. Med J Aust. 2008;188(1):26–8.