Skip to main content
Log in

Zoledronic Acid

A Pharmacoeconomic Review of its Use in the Management of Bone Metastases

  • Adis Pharmacoeconomic Drug Evaluation
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Table II
Table III
Table IV
Table V

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Coleman RE. Should bisphosphonates be the treatment of choice for metastatic bone disease? Semin Oncol 2001 Aug; 28 (4 Suppl. 11): 35–41

    Article  PubMed  CAS  Google Scholar 

  2. Lipton A. Management of metastatic bone disease and hypercalcemia of malignancy. Am J Cancer 2003; 2: 427–38

    Article  Google Scholar 

  3. Cameron D. Patient management issues in metastatic bone disease. Semin Oncol 2004 Oct; 31 (5 Suppl. 10): 79–82

    Article  PubMed  Google Scholar 

  4. 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

    PubMed  CAS  Google Scholar 

  5. Yuen KK, Shelley M, Sze WM, et al. Bisphosphonates for advanced prostate cancer. Cochrane Database Syst Rev 2006 Oct 18; (4): CD006250

    Google Scholar 

  6. Pavlakis N, Schmidt RL, Stockier M. Bisphosphonates for breast cancer. Cochrane Database Syst Rev 2005 Jul; (3): CD003474

    Google Scholar 

  7. 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

    Article  PubMed  CAS  Google Scholar 

  8. 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

    Article  PubMed  CAS  Google Scholar 

  9. 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

    Article  PubMed  CAS  Google Scholar 

  10. 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

    Article  PubMed  CAS  Google Scholar 

  11. Zometa® (zoledronic acid injection): US prescribing information. East Hanover (NJ): Novartis Pharmaceuticals Corporation, 2007 Sep

  12. Coleman RE. Skeletal complications of malignancy. Cancer 1997 Oct 15; 80 (8 Suppl.): 1588–94

    Article  PubMed  CAS  Google Scholar 

  13. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 (2): 74–108

    Article  PubMed  Google Scholar 

  14. 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

    PubMed  Google Scholar 

  15. 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

    Article  PubMed  CAS  Google Scholar 

  16. 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

    Article  Google Scholar 

  17. 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

    Article  PubMed  CAS  Google Scholar 

  18. Perry CM, Figgitt DP. Zoledronic acid: a review of its use in patients with advanced cancer. Drugs 2004; 64 (11): 1197–211

    Article  PubMed  CAS  Google Scholar 

  19. 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

    Article  PubMed  CAS  Google Scholar 

  20. 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

    Article  PubMed  CAS  Google Scholar 

  21. 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

    Article  PubMed  CAS  Google Scholar 

  22. 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

    Google Scholar 

  23. 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

    Article  Google Scholar 

  24. Krueger CD, West PM, Sargent M, et al. Bisphosphonate-induced osteonecrosis of the jaw. Ann Pharmacother 2007 Feb; 41 (2): 276–84

    Article  PubMed  CAS  Google Scholar 

  25. 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

    Article  PubMed  Google Scholar 

  26. 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

    Article  PubMed  CAS  Google Scholar 

  27. 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

    Article  PubMed  Google Scholar 

  28. 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

    Article  PubMed  Google Scholar 

  29. 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

    Article  PubMed  Google Scholar 

  30. 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

    Article  Google Scholar 

  31. 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

    Google Scholar 

  32. 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

    Google Scholar 

  33. 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

    Google Scholar 

  34. 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

    Google Scholar 

  35. 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

    Article  PubMed  Google Scholar 

  36. 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

    Article  PubMed  CAS  Google Scholar 

  37. 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

    Google Scholar 

  38. 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

    Article  Google Scholar 

  39. 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

    Article  Google Scholar 

  40. 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

    Article  PubMed  CAS  Google Scholar 

  41. 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

    PubMed  CAS  Google Scholar 

  42. 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

    Article  PubMed  Google Scholar 

  43. 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

    Article  PubMed  CAS  Google Scholar 

  44. 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

    PubMed  CAS  Google Scholar 

  45. 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

    Article  PubMed  CAS  Google Scholar 

  46. Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer 1987; 55 (1): 61–6

    Article  PubMed  CAS  Google Scholar 

  47. Andersen PK, Gill RD. Cox’s regression model for counting processes: a large sample study. Ann Stat 1982; 10 (4): 1100–20

    Article  Google Scholar 

  48. 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

    Article  PubMed  Google Scholar 

  49. 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

    Article  PubMed  CAS  Google Scholar 

  50. 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

    Article  Google Scholar 

  51. 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

    Article  PubMed  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  53. Jönsson B. Changing health environment: the challenge to demonstrate cost-effectiveness of new compounds. Pharmacoeconomics 2004; 22 Suppl. 4: 5–10

    Article  PubMed  Google Scholar 

  54. 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

    Article  Google Scholar 

  55. Major PP, Lipton A, Berenson J, et al. Oral bisphosphonates. Cancer 2000; 88 (1): 6–14

    Article  PubMed  CAS  Google Scholar 

  56. 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

    Article  PubMed  CAS  Google Scholar 

  57. 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

    Google Scholar 

  58. 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

    Article  PubMed  CAS  Google Scholar 

  59. Aredia® (pamidronate disodium for injection): US prescribing information. East Hanover (NJ): Novartis Pharmaceuticals Corporation, 2007

  60. Gralow J, Tripathy D. Managing metastatic bone pain: the role of bisphosphonates. J Pain Symptom Manage 2007; 33 (4): 462–72

    Article  PubMed  CAS  Google Scholar 

  61. 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

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kate McKeage.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McKeage, K., Plosker, G.L. Zoledronic Acid. Pharmacoeconomics 26, 251–268 (2008). https://doi.org/10.2165/00019053-200826030-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00019053-200826030-00007

Keywords

Navigation