Cost-Effectiveness Analyses of Targeted Oral Anti-Cancer Drugs: A Systematic Review
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Over the last 15 years, a paradigm shift in oncology has led to the approval of dozens of targeted oral anti-cancer medications (OAMs), which have become the standard of care for certain cancers. While more convenient for patients than infused drugs, the possibility of non-adherence and the frequently high costs of targeted OAMs have proven controversial.
Our objective was to perform the first comprehensive review of cost-effectiveness analyses (CEAs) of targeted OAMs.
A literature search in PubMed, The Cochrane Library, and the Health Technology Assessment (HTA) reports published by the National Institute for Health Research HTA Programme in the UK was performed, covering articles published in the 5 years prior to 30 September 2013. Our inclusion criteria were peer-reviewed English-language full-text original research articles with a primary focus on CEA related to targeted OAMs. We categorized these articles by treatment setting (i.e. cancer site/type, line of therapy, and treatment and comparator) and synthesized information from the articles into summary tables.
We identified 41 CEAs covering nine of the 18 targeted OAMs approved by the US FDA as of December 2012. These medications were studied in seven cancers, most often as second-line therapy for advanced-stage patients. In over half of treatment settings where a targeted OAM was compared with treatment that was not a targeted OAM, targeted OAMs were considered cost effective. Limitations in interpreting these findings include the risk of bias due to author conflicts of interest, cross-country variation, and difficulties in generalizing clinical trial evidence to community practice.
Several types of cost-effectiveness studies remain under-represented in the literature on targeted OAMs, including those for follow-on indications approved after the initial indication for a drug and for off-label indications, head-to-head comparisons of targeted OAMs with other targeted OAMs and targeted intravenous therapies, and studies that adopt a perspective other than the payer’s. Keeping up with the increasing number of approved targeted OAMs will also prove an important challenge for economic evaluation.
- 5.Weingart SN, Brown E, Bach PB, Eng K, Johnson SA, Kuzel TM, et al. NCCN Task Force Report: Oral chemotherapy. J Natl Compr Cancer Netw. 2008;6(Suppl 3):S1–14.Google Scholar
- 9.Rao RD, Cobleigh MA. Adjuvant endocrine therapy for breast cancer. Oncology. 2012;26(6):541–7, 50, 52 passim.Google Scholar
- 11.Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.CrossRefPubMedGoogle Scholar
- 18.Shen C, Chien C-R, Geynisman DM, Smieliauskas F, Shih Y-CT. A review of economic impact of targeted oral anticancer medications. Expert Rev Pharmacoecon Outcomes Res. 2014;14(1):45-69Google Scholar
- 21.Drummond M, Evans B, LeLorier J, Karakiewicz P, Martin D, Tugwell P, et al. Evidence and values: requirements for public reimbursement of drugs for rare diseases—a case study in oncology. Can J Clin Pharmacol 2009 Summer;16(2):e273–81; discussion e82–4.Google Scholar
- 25.HIRU. Search Filters for MEDLINE in Ovid Syntax and the PubMed translation. [cited 2013 September 3]. http://hiru.mcmaster.ca/hiru/HIRU_Hedges_MEDLINE_Strategies.aspx.
- 26.BLS. Consumer Price Index. [cited 2013 November 14]. http://www.bls.gov/cpi/.
- 27.IMF. World Economic Outlook Database. [cited 2013 December 7]. http://www.imf.org/external/pubs/ft/weo/2009/02/weodata/index.aspx.
- 29.NCI. Cancer Drug Information. [cited 2013 December 7]. http://www.cancer.gov/cancertopics/druginfo/alphalist.
- 31.Machado M, Einarson TR. Lapatinib in patients with metastatic breast cancer following initial treatment with trastuzumab: an economic analysis from the Brazilian public health care perspective. Breast Cancer (Dove Med Press). 2012;2012(4):173–82.Google Scholar
- 34.Experts in Chronic Myeloid Leukemia, The price of drugs for chronic myeloid leukemia. (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood. 2013;121(22):4439–42.Google Scholar
- 37.Chen Z, Wang C, Xu X, Feng W. Cost-effectiveness study comparing imatinib with interferon-alpha for patients with newly diagnosed chronic-phase (CP) chronic myeloid leukemia (CML) from the Chinese public health-care system perspective (CPHSP). Value Health. 2009;12 Suppl 3:S85–8.Google Scholar
- 39.Ghatnekar O, Hjalte F, Taylor M. Cost-effectiveness of dasatinib versus high-dose imatinib in patients with Chronic Myeloid Leukemia (CML), resistant to standard dose imatinib—a Swedish model application. Acta Oncol. 2010;49(6):851–8.Google Scholar
- 40.Patel SR, Wong P. The efficacy of imatinib in unresectable/metastatic gastrointestinal stromal tumors. US Oncol Rev. 2009;5(1):61–4.Google Scholar
- 42.Majer IM, Gelderblom H, van den Hout WB, Gray E, Verheggen BG. Cost-effectiveness of 3-year vs 1-year adjuvant therapy with imatinib in patients with high risk of gastrointestinal stromal tumour recurrence in the Netherlands; a modelling study alongside the SSGXVIII/AIO trial. J Med Econ. 2013;16(9):1106–19.CrossRefPubMedGoogle Scholar
- 44.Paz-Ares L, Garcia del Muro X, Grande E, Gonzalez P, Brosa M, Diaz S. Cost-effectiveness analysis of sunitinib in patients with metastatic and/or unresectable gastrointestinal stroma tumours (GIST) after progression or intolerance with imatinib. Clin Transl Oncol. 2008;10(12):831–9.Google Scholar
- 45.Contreras-Hernandez I, Mould-Quevedo JF, Silva A, Salinas-Escudero G, Villasis-Keever MA, Granados-Garcia V, et al. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours. Br J Cancer. 2008;98(11):1762–8.PubMedCentralCrossRefPubMedGoogle Scholar
- 46.Vitale A, Volk ML, Pastorelli D, Lonardi S, Farinati F, Burra P, et al. Use of sorafenib in patients with hepatocellular carcinoma before liver transplantation: a cost-benefit analysis while awaiting data on sorafenib safety. Hepatology. 2010;51(1):165–73.Google Scholar
- 49.Camma C, Cabibbo G, Petta S, Enea M, Iavarone M, Grieco A, et al. Cost-effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma. Hepatology. 2013;57(3):1046–54.Google Scholar
- 50.ALA (American Lung Association). Lung Cancer Fact Sheet. 2013 [cited 2013 November 17]. http://www.lung.org/lung-disease/lung-cancer/resources/facts-figures/lung-cancer-fact-sheet.html.
- 51.Chouaid C, Le Caer H, Locher C, Dujon C, Thomas P, Auliac JB, et al. Cost-effectiveness of erlotinib versus chemotherapy for first-line treatment of non small cell lung cancer (NSCLC) in fit elderly patients participating in a prospective phase 2 study (GFPC 0504). BMC Cancer. 2012;12:301.CrossRefPubMedGoogle Scholar
- 52.Chouaid C, Le Caer H, Corre R, Crequit J, Locher C, Falchero L, et al. Cost analysis of erlotinib versus chemotherapy for first-line treatment of non-small-cell lung cancer in frail elderly patients participating in a prospective phase 2 study (GFPC 0505). Clin Lung Cancer. 2013;14(2):103–7.CrossRefPubMedGoogle Scholar
- 53.Wang S, Peng L, Li J, Zeng X, Ouyang L, Tan C, et al. A trial-based cost-effectiveness analysis of erlotinib alone versus platinum-based doublet chemotherapy as first-line therapy for Eastern Asian nonsquamous non-small-cell lung cancer. PloS One. 2013;8(3):e55917.PubMedCentralCrossRefPubMedGoogle Scholar
- 58.Lewis G, Peake M, Aultman R, Gyldmark M, Morlotti L, Creeden J, et al. Cost-effectiveness of erlotinib versus docetaxel for second-line treatment of advanced non-small-cell lung cancer in the United Kingdom. J Int Med Res. 2010;38(1):9–21.Google Scholar
- 60.Carlson JJ, Reyes C, Oestreicher N, Lubeck D, Ramsey SD, Veenstra DL. Comparative clinical and economic outcomes of treatments for refractory non-small cell lung cancer (NSCLC). Lung Cancer. 2008;61(3):405–15.Google Scholar
- 61.Araujo A, Parente B, Sotto-Mayor R, Teixeira E, Almodovar T, Barata F, et al. An economic analysis of erlotinib, docetaxel, pemetrexed and best supportive care as second or third line treatment of non-small cell lung cancer. Rev Port Pneumol. 2008;14(6):803–27.Google Scholar
- 64.Cromwell I, van der Hoek K, Malfair Taylor SC, Melosky B, Peacock S. Erlotinib or best supportive care for third-line treatment of advanced non-small-cell lung cancer: a real-world cost-effectiveness analysis. Lung Cancer. 2012;76(3):472–7.Google Scholar
- 69.Calvo Aller E, Maroto P, Kreif N, Gonzalez Larriba JL, Lopez-Brea M, Castellano D, et al. Cost-effectiveness evaluation of sunitinib as first-line targeted therapy for metastatic renal cell carcinoma in Spain. Clin Transl Oncol. 2011;13(12):869–77.Google Scholar
- 72.Paz-Ares L, del Muro JG, Grande E, Diaz S. A cost-effectiveness analysis of sunitinib in patients with metastatic renal cell carcinoma intolerant to or experiencing disease progression on immunotherapy: perspective of the Spanish National Health System. J Clin Pharmacy Ther. 2010;35(4):429–38.Google Scholar
- 73.Hoyle M, Green C, Thompson-Coon J, Liu Z, Welch K, Moxham T, et al. Cost-effectiveness of sorafenib for second-line treatment of advanced renal cell carcinoma. Value Health. 2010;13(1):55–60.Google Scholar
- 74.Casciano R, Chulikavit M, Di Lorenzo G, Liu Z, Baladi JF, Wang X, et al. Economic evaluation of everolimus versus sorafenib for the treatment of metastatic renal cell carcinoma after failure of first-line sunitinib. Value Health. 2011;14(6):846–51.Google Scholar
- 75.Tam VC, Ko YJ, Mittmann N, Cheung MC, Kumar K, Hassan S, et al. Cost-effectiveness of systemic therapies for metastatic pancreatic cancer. Curr Oncol. 2013;20(2):e90–e106.Google Scholar
- 77.IOM (Institute of Medicine). Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis. Washington, DC: The National Academies Press; 2013.Google Scholar
- 80.OECD. Cancer care: assuring quality to improve survival. OECD Health Policy Studies, OECD Publishing, 2013. http://dx.doi.org/10.1787/9789264181052-en.
- 83.Danzon PM, Furukawa MF. International prices and availability of pharmaceuticals in 2005. Health Aff (Millwood). 2008;27(1):221–33.Google Scholar
- 84.Squires DA. The U.S. health system in perspective: a comparison of twelve industrialized nations. Issue Brief (Commonw Fund). 2011;16:1–14Google Scholar
- 85.IOM (Institute of Medicine). Observational Studies in a Learning Health System: Workshop Summary. Washington, DC: The National Academies Press; 2013.Google Scholar
- 86.Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. Oxford: Oxford University Press; 1996.Google Scholar
- 87.American Cancer Society. Cancer Facts & Figures 2013. Atlanta, GA: American Cancer Society; 2013.Google Scholar
- 91.Drummond MF, Sculpher MJ, Torrance GW, O’Brien BJ, Stoddart GL. Methods for the economic evaluation of health care programmes. 3rd ed. New York: Oxford University Press; 2005.Google Scholar
- 92.Zafar SY, Abernethy AP. Financial toxicity, Part II: how can we help with the burden of treatment-related costs? Oncology. 2013;27(4):253–4, 6.Google Scholar
- 93.Zafar SY, Abernethy AP. Financial toxicity, Part I: a new name for a growing problem. Oncology. 2013;27(2):80–1, 149.Google Scholar
- 95.IOM (Institute of Medicine). Facilitating collaborations to develop combination investigational cancer therapies: workshop summary. Washington, DC: The National Academies Press; 2012.Google Scholar