Real-World Evidence: A Comparison of the Australian Herceptin Program and Clinical Trials of Trastuzumab for HER2-Positive Metastatic Breast Cancer
- 634 Downloads
Estimating the real-world cost-effectiveness of a new drug relies on understanding the differences between clinical trial data (pre-reimbursement) and clinical practice (post-reimbursement). This is important for decision makers when reviewing reimbursement decisions, prices, and considering other drugs for the same condition. Differences can arise from differences in patient characteristics, but also from the availability of new evidence and evolving treatment practices. This paper examines these issues using a case study.
In 2001, the Australian Government funded trastuzumab for the treatment of HER2+ metastatic breast cancer through the Herceptin Program. The administrative arrangements of the Program resulted in rich observational data that captured information about patients treated with trastuzumab between 2001 and 2010 (n = 3830). The dataset included patient characteristics, dispensed medicines, medical service use and date of death.
Compared to participants in the clinical trials, patients were older, received more prior chemotherapies and a broader range of co-administered chemotherapies. Treatment practices differed from the clinical trials, but also changed over time. For example, in situ hybridization testing, rather than immunohistochemistry testing, and a three weekly administration schedule, rather than one weekly, were increasingly used. Compared to the clinical trials, patients administered trastuzumab with a concomitant chemotherapy generally experienced longer overall survival (151.3 weeks, 95 % CI: 142.6, 163.4), while those who received trastuzumab as a monotherapy experienced shorter overall survival (94.4 weeks, 95%CI: 86.4, 102.9). These findings may be due to a differing relative treatment effect in clinical practice, but may also be due to a range of other factors.
This analysis demonstrates the challenges for decision makers that arise because new evidence and evolving treatment practices create a gap between clinical trial data and real-world clinical practice and outcomes.
KeywordsTrastuzumab Vinorelbine Pharmaceutical Benefit Scheme Concomitant Chemotherapy Reimbursement Decision
Bonny Parkinson, Rosalie Viney and Sallie-Anne Pearson contributed to the conception of the paper. Bonny Parkinson conducted the data analyses, with advice from the other co-authors. All co-authors contributed towards drafting and revising the intellectual content of the manuscript, and approved the final version for publication.
Compliances with Ethical Standards
Conflict of interest
Bonny Parkinson, Marion Haas, Stephen Goodall and Preeyaporn Srasuebkul have no conflicts of interest to declare. Sallie-Anne Pearson is a member of the Drug Utilisation Sub-Committee of the Australian Pharmaceutical Benefits Advisory Committee (PBAC). Rosalie Viney is a member of PBAC and its Economics Sub-Committee. The content of this paper does not reflect the views of the Australian Government Department of Health, the PBAC or its Sub-Committees.
The research reported in this paper is supported by an Australian National Health and Medical Research Council (NHMRC) Capacity Building Grant in Health Services Research (NHMRC ID: 571926), an Australian NHMRC Centre of Research Excellence in Medicines and Ageing Grant (ID: 1060407) and a Cancer Australia Grant (ID: 568773).
- 3.Ferrario A, Kanavos P. Managed entry agreements for pharmaceuticals: the European experience. Brussels: EMiNet; 2013.Google Scholar
- 4.Pharmaceutical Benefits Advisory Committee. Public summary document: pembrolizumab, 50 mg vial, 100 mg vial, Keytruda. Canberra: DoH; 2015.Google Scholar
- 6.Annemans L, Aristides M, Kubin M. Real-life data: a growing need. ISPOR Connect. 2007;13(5):8–12.Google Scholar
- 11.Claxton K, Palmer S, Longworth L, Bojke L, Griffin S, McKenna C, et al. Informing a decision framework for when NICE should recommend the use of health technologies only in the context of an appropriately designed programme of evidence development. Health Technol Assess. 2012;16(46):1–323.CrossRefPubMedGoogle Scholar
- 12.Pharmaceutical Benefits Advisory Committee. Public summary document: crizotinib, 200 mg capsule, 60 and 250 mg capsule, 60, Xalkori. Canberra: DoH; 2014.Google Scholar
- 13.Medical Services Advisory Committee. Tests for HER2 gene amplification in breast cancer, assessment report, MSAC reference no. 38. Canberra: DoHA; 2008.Google Scholar
- 16.Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005;23(19):4265–74.CrossRefPubMedGoogle Scholar
- 17.Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009;27(33):5529–37.CrossRefPubMedGoogle Scholar
- 18.Gasparini G, Gion M, Mariani L, Papaldo P, Crivellari D, Filippelli G, et al. Randomized phase II trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with HER-2 positive advanced breast cancer. Breast Cancer Res Treat. 2007;101(3):355–65.CrossRefPubMedGoogle Scholar
- 19.Andersson M, Lidbrink E, Bjerre K, Wist E, Enevoldsen K, Jensen AB, et al. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol. 2011;29(3):264–71.CrossRefPubMedGoogle Scholar
- 21.Pharmaceutical Benefits Advisory Committee. Public summary document: trastuzumab, powder for IV infusion, 150 mg, Herceptin. Canberra: DoHA; 2008.Google Scholar
- 22.McGrath C. Politicians inundated by breast cancer survivors. The World Today, ABC local radio [transcript]. Sydney: ABC; 2001. http://www.abc.net.au/worldtoday/stories/s358933.htm. Accessed 28 Apr 2016.
- 23.Cresswell A. Life or death rations. The Australian. 2009. http://www.theaustralian.com.au/opinion/life-or-death-rations/story-e6frg6zo-1225779703837. Accessed 28 Apr 2016.
- 26.Fabi A, Metro G, Ferretti G, Giannarelli D, Di Cosimo S, Papaldo P, et al. Do HER-2 positive metastatic breast cancer patients benefit from the use of trastuzumab beyond disease progression? A mono-institutional experience and systematic review of observational studies. Breast. 2008;17(5):499–505.CrossRefPubMedGoogle Scholar
- 29.Extra JM, Antoine EC, Vincent-Salomon A, Delozier T, Kerbrat P, Bethune-Volters A, et al. Efficacy of trastuzumab in routine clinical practice and after progression for metastatic breast cancer patients: the observational Hermine study. Oncologist. 2010;15(8):799–809.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Poncet B, Colin C, Bachelot T, Jaisson-Hot I, Derain L, Magaud L, et al. Treatment of metastatic breast cancer: a large observational study on adherence to French prescribing guidelines and financial cost of the anti-HER2 antibody trastuzumab. Am J Clin Oncol. 2009;32(4):369–74.CrossRefPubMedGoogle Scholar
- 33.Joshi V, Pearson SA, Adelstein BA, Faedo M, Srasuebkul P, Dobbins T. Estimating disease progression using prescribing data in patients with metastatic disease: a pilot validation study, Independent Learning Project. Sydney: University of New South Wales; 2011.Google Scholar
- 34.Joshi V, Adelstein BA, Schaffer A, Srasuebkul P, Investigators EoCC, Dobbins T, et al. A proxy of cancer progression in dispensing claims: validation and performance [abstract no. 450]. Pharmacoepidemiol Drug Saf. 2013;22(S1):221–2.Google Scholar
- 35.Joshi V, Adelstein BA, Srasuebkul P, Schaffer A, Dobbins T, Pearson SA. Estimating disease progression in metastatic cancer patients using dispensing data: a validation study [abstract no. 359]. Pharmacoepidemiol Drug Saf. 2012;21(S3):169.Google Scholar
- 36.Australian Government, Department of Human Services. Late stage metastatic breast cancer. http://www.medicareaustralia.gov.au/provider/patients/late-breast-cancer.jsp. Accessed 17 Oct 2011
- 38.Australian Government Department of Health and Ageing (DoHA). Schedule of Pharmaceutical Benefits, efficient funding of chemotherapy—section 100 arrangements supplement, effective 1 January 2013. Canberra: DoHA; 2013.Google Scholar
- 40.Center for Biologics Evaluation and Research. Trastuzumab, herceptin (rhuMAbHER2): clinical review briefing document. Maryland: US Food and Drug Administration; 2001.Google Scholar
- 44.Commonwealth Government of Australia. Budget 2011–12, mid-year economic and fiscal outlook, Appendix A. Canberra: Department of Finance; 2011.Google Scholar
- 45.Medical Services Advisory Committee. HER2 ISH testing for access to trastuzumab for neoadjuvant breast cancer, public summary document, MSAC application no. 1230. Canberra: DoHA; 2012.Google Scholar