Abstract
Zoledronic acid (Zometa®) is a third-generation nitrogen-containing parenteral bisphosphonate indicated for the treatment of bone metastases due to solid tumours or multiple myeloma and for hypercalcaemia of malignancy (HCM). In patients with advanced breast or prostate cancer, zoledronic acid 4 mg every 3–4 weeks for up to 15 months significantly reduced the proportion of patients with ≥1 skeletal-related event (SRE), excluding HCM, compared with placebo. In patients with advanced breast cancer or multiple myeloma, the incidence of SREs was similar in patients treated with zoledronic acid 4 mg or pamidronic acid 90 mg every 3–4 weeks for up to 25 months but, in breast cancer patients, zoledronic acid reduced the risk of SREs, including HCM, by an additional 20% compared with pamidronic acid.
In modelled cost-utility studies comparing direct costs based on efficacy and resource-use data from these and/or other trials, results have varied. In the most recent study performed from the perspective of the UK NHS and modelled over a 10-year treatment period in women with advanced breast cancer, intravenous zoledronic acid and oral ibandronic acid were dominant over no treatment. Intravenous zoledronic acid was the most cost effective, in terms of incremental costs per QALY gained, followed by oral ibandronic acid, intravenous pamidronic acid and intravenous ibandronic acid. Two other modelled analyses in patients with advanced breast cancer, also conducted from the perspective of the NHS, evaluated the cost utility of three bisphosphonate therapies in patients receiving hormonal therapy or intravenous chemotherapy. Analyses were modelled over 14.3 months (i.e. expected survival) and assumptions varied markedly from results in clinical breast cancer trials. Also, efficacy assumptions for zoledronic acid were not based on clinical trials with the drug. The results of these analyses suggest that oral ibandronic acid is more cost effective than intravenous zoledronic acid and intravenous pamidronic acid in terms of incremental cost per QALY gained.
In a global, 15-month modelled cost-effectiveness analysis of patients with advanced prostate cancer, conducted from a third-party perspective, the incremental cost per QALY gained for zoledronic acid versus no treatment was $US159 200 (year 2000 value), which is about 3-fold greater than commonly accepted thresholds for cost effectiveness.
In conclusion, a recent modelled economic analysis suggests that intravenous zoledronic acid 4 mg is dominant relative to no treatment in the management of bone metastases in patients with advanced breast cancer. In contrast, in patients with advanced prostate cancer, the incremental cost per QALY gained for zoledronic acid 4 mg versus no treatment was predicted to be higher than commonly accepted thresholds. Compared with other bisphosphonates in the setting of advanced breast cancer, intravenous zoledronic acid was more cost effective than oral or intravenous ibandronic acid and intravenous pamidronic acid in one study, but less cost effective than oral ibandronic acid in another. Further efficacy and economic data comparing intravenous zoledronic acid with oral ibandronic acid are needed. Meanwhile, zoledronic acid appears to be the most cost effective intravenous bisphosphonate for the management of bone metastases in patients with advanced breast cancer and possibly in patients with different types of advanced solid tumours.
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References
Coleman RE. Should bisphosphonates be the treatment of choice for metastatic bone disease? Semin Oncol 2001 Aug; 28 (4 Suppl. 11): 35–41
Lipton A. Management of metastatic bone disease and hypercalcemia of malignancy. Am J Cancer 2003; 2: 427–38
Cameron D. Patient management issues in metastatic bone disease. Semin Oncol 2004 Oct; 31 (5 Suppl. 10): 79–82
Ross JR, Saunders Y, Edmonds PM, et al. A systematic review of the role of bisphosphonates in metastatic disease. Health Technol Assess 2004; 8 (4): 1–176
Yuen KK, Shelley M, Sze WM, et al. Bisphosphonates for advanced prostate cancer. Cochrane Database Syst Rev 2006 Oct 18; (4): CD006250
Pavlakis N, Schmidt RL, Stockier M. Bisphosphonates for breast cancer. Cochrane Database Syst Rev 2005 Jul; (3): CD003474
Hillner BE, Ingle JN, Chlebowski RT, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003; 21 (21): 4042–57
Saad F, Gleason DM, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002 Oct 2; 94 (19): 1458–68
Brown JE, Cook RJ, Major P, et al. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumours. J Natl Cancer Inst 2005; 97 (1): 59–69
McCloskey EV, Guest JF, Kanis JA. The clinical and cost considerations of bisphosphonates in preventing bone complications in patients with metastatic breast cancer or multiple myeloma. Drugs 2001; 61 (9): 1253–74
Zometa® (zoledronic acid injection): US prescribing information. East Hanover (NJ): Novartis Pharmaceuticals Corporation, 2007 Sep
Coleman RE. Skeletal complications of malignancy. Cancer 1997 Oct 15; 80 (8 Suppl.): 1588–94
Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 (2): 74–108
Delea T, McKiernan J, Brandman J, et al. Retrospective study of the effect of skeletal complications on total medical care costs in patients with bone metastases of breast cancer seen in typical clinical practice. J Support Oncol 2006; 4 (7): 341–7
Groot MT, Boeken Kmger CG, Pelger RC, et al. Costs of prostate cancer, metastatic to the bone, in the Netherlands. Eur Urol 2003 Mar; 43 (3): 226–32
Groot MT, Huijgens PC, Wijermans PJ, et al. Costs of multiple myeloma and associated skeletal-related events in The Netherlands. Expert Rev Pharmacoeconomics Outcomes Res 2004; 4 (5): 565–72
Wellington K, Goa KL. Zoledronic acid: a review of its use in the management of bone metastases and hypercalcaemia of malignancy. Drugs 2003; 63 (4): 417–37
Perry CM, Figgitt DP. Zoledronic acid: a review of its use in patients with advanced cancer. Drugs 2004; 64 (11): 1197–211
Kohno N, Aogi K, Minami H, et al. Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol 2005 May 20; 23 (15): 3314–21
Rosen LS, Gordon D, Kaminski M, et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 2003 Oct 15; 98 (8): 1735–44
Rosen LS, Gordon D, Tchekmedyian NS, et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, phase III, double-blind, placebo-controlled trial. Cancer 2004 Jun 15; 100 (12): 2613–21
Dimopoulos M, Berenson J, Shirina Y, et al. Survival in patients with multiple myeloma receiving zoledronic acid: statification by baseline bone alkaline phosphatase levels [abstract no. 7505]. J Clin Oncol 2006; 24 (18 Suppl.): 423S
Lipton A, Colombo-Berra A, Bukowski RM, et al. Skeletal complications in patients with bone metastases from renal cell carcinoma and therapeutic benefits of zoledronic acid. Clin Cancer Res 2004 Sep 15; 10 Suppl.: 6397–403
Krueger CD, West PM, Sargent M, et al. Bisphosphonate-induced osteonecrosis of the jaw. Ann Pharmacother 2007 Feb; 41 (2): 276–84
Wang EP, Kaban LB, Strewler GJ, et al. Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg 2007 Jul; 65 (7): 1328–31
Botteman M, Barghout V, Stephens J, et al. Cost effectiveness of bisphosphonates in the management of breast cancer patients with bone metastases. Ann Oncol 2006 Jul; 17 (7): 1072–82
De Cock E, Hutton J, Canney P, et al. Cost-effectiveness of oral ibandronate versus iv zoledronic acid or iv pamidronate for bone metastases in patients receiving oral hormonal therapy for breast cancer in the United Kingdom. Clin Ther 2005 Aug; 27 (8): 1295–310
De Cock E, Hutton J, Canney P, et al. Cost-effectiveness of oral ibandronate compared with intravenous (i.v.) zoledronic acid or i.v. generic pamidronate in breast cancer patients with metastatic bone disease undergoing i.v. chemotherapy. Support Care Cancer 2005 Dec; 13 (12): 975–86
Reed SD, Radeva JI, Glendenning GA, et al. Cost-effectiveness of zoledronic acid for the prevention of skeletal complications in patients with prostate cancer. J Urol 2004 Apr; 171 (4): 1537–42
Botteman M, Hay J, Stephens JM, et al. Cost effectiveness model of IV bisphosphonates in the prevention of bone complications in breast cancer patients with bone metastases: a German inpatient perspective [abstract no. PCN31]. Value Health 2005; 8 (6): A42–3
Botteman M, Hay JW, Stephens JM, et al. A markov model to evaluate the cost effectiveness of five bisphosphonate therapies in the prevention of bone complications in breast cancer patients with bone metastases: a German outpatient perspective [abstract no. 423]. EJC Supplements 2005; 3 (2): 119
El Ouagari L, Botteman M, Aapro M, et al. Cost-effectiveness of zoledronic acid vs. other bisphosphonate agents for the prevention of bone complications in breast cancer: an application to Canada [abstract no. 418]. EJC Supplements 2005; 3 (2): 117
Botteman MF, Foley I, Marfatia AA, et al. Economic value of zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer: the case in the United Kingdom (UK) [abstract no. 6617]. J Clin Oncol 2007 Jun 20; 25 (18 Suppl.): 351
Botteman M, Foley I, Marfatia A, et al. Zoledronic acid is cost saving and improves quality-adjusted survival in the prevention of skeletal related events in patients with bone metastases secondary to advanced renal cell carcinoma: a German perspective [abstract no. 4515]. EJC Supplements 2007; 5 (4 Suppl.): 303. Plus poster presented at the 14th European Cancer Conference; 2007 Sep 23–27; Barcelona
Reed SD, Radeva JI, Glendenning GA, et al. Economic evaluation of zoledronic acid versus pamidronate for the prevention of skeletal-related events in metastatic breast cancer and multiple myeloma. Am J Clin Oncol 2005 Feb; 28 (1): 8–16
Guest JF, Clegg JP, Davie AM, et al. Costs and consequences of using pamidronate compared with zoledronic acid in the management of breast cancer patients in the UK. Curr Med Res Opin 2005 May; 21 (5): 805–15
Gammon DC, Le HT. Zoledronic acid vs pamidronate for the prevention of hypercalcemia of malignancy or bone metastases in hospital outpatients: time analysis and economic implications. Hosp Pharm 2003; 38 (12): 1148–50
DesHarnais Castel L, Bajwa K, Markle JP, et al. A microcosting analysis of zoledronic acid and pamidronate therapy in patients with metastatic bone disease. Support Care Cancer 2001 Oct; 9 (7): 545–51
Tripathy D, Budde M. Assessing the efficacy of ibandronate for the prevention of skeletal-related events (SREs) in metastatic bone disease: a methodological comparison [abstract no. 76]. Bone 2004; 34: S91–2
Lipton A, Theriault RL, Hortobagyi GN, et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomised, placebo-controlled trials. Cancer 2000; 88: 1082–90
Paterson AHG, Powles TJ, Kanis JA, et al. Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer. J Clin Oncol 1993; 11: 59–65
Body J J, Diel I J, Lichinitzer MR. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann Oncol 2003; 14: 1399–405
Body JJ, Diel I J, Lichinitzer M, et al. Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomised, placebo-controlled phase III studies. Br J Cancer 2004; 90: 1133–7
Hillner BE, Weeks JC, Desch CE, et al. Pamidronate in prevention of bone complications in metastatic breast cancer: a cost-effectiveness analysis. J Clin Oncol 2000; 18 (1): 72–9
Dranitsaris G, Hsu T. Cost utility analysis of prophylactic pamidronate for the prevention of skeletal related events in patients with advanced breast cancer. Support Care Cancer 1999; 7: 271–9
Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer 1987; 55 (1): 61–6
Andersen PK, Gill RD. Cox’s regression model for counting processes: a large sample study. Ann Stat 1982; 10 (4): 1100–20
Weinfurt KP, Castel LD, Li Y, et al. Health-related quality of life among patients with breast cancer receiving zoledronic acid or pamidronate disodiumfor metastatic bone lesions. Med Care 2004 Feb; 42 (2): 164–75
Wardley A, Davidson N, Barrett-Lee P, et al. Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration. Br J Cancer 2005 May 23; 92 (10): 1869–76
Göl D, Höer A, Brandman J. Poor persistency with oral bisphosphonates in cancer patients with bone metastasis. Cancer Treat Rev 2005; 31 Suppl. 1: 49–50
Devlin N, Parkin D. Does NICE have a cost-effectiveness threshold and what other factors influence its decisions? A binary choice analysis. Health Econ 2004; 13: 437–52
Rosen LS, Gordon D, Antonio BS, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 2001 Sep 31; 7 (5): 377–87
Jönsson B. Changing health environment: the challenge to demonstrate cost-effectiveness of new compounds. Pharmacoeconomics 2004; 22 Suppl. 4: 5–10
Kyle RA, Yee GC, Somerfield MR, et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 2007; 25 (17): El–9
Major PP, Lipton A, Berenson J, et al. Oral bisphosphonates. Cancer 2000; 88 (1): 6–14
McCormack PL, Plosker GL. Ibandronic acid: a review of its use in the treatment of bone metastases of breast cancer. Drugs 2006; 66 (5): 711–28
Mangiapane S, Hoer A, Gother H, et al. Higher persistency with i.v. bisphosphonates in patients with bone metastasis [abstract no. 18623]. J Clin Oncol 2006; 24 (18 Suppl.): 1
Chern B, Joseph D, Joshua D, et al. Bisphosphonate infusions: patient preference, safety and clinic use. Support Care Cancer 2004 Jun; 12 (6): 463–6
Aredia® (pamidronate disodium for injection): US prescribing information. East Hanover (NJ): Novartis Pharmaceuticals Corporation, 2007
Gralow J, Tripathy D. Managing metastatic bone pain: the role of bisphosphonates. J Pain Symptom Manage 2007; 33 (4): 462–72
Pectasides D, Nikolaou M, Farmakis D, et al. Clinical value of bone remodelling markers in patients with bone metastases treated with zoledronic acid. Anticancer Res 2005; 25: 1457–63
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McKeage, K., Plosker, G.L. Zoledronic Acid. Pharmacoeconomics 26, 251–268 (2008). https://doi.org/10.2165/00019053-200826030-00007
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DOI: https://doi.org/10.2165/00019053-200826030-00007