Skip to main content

Advertisement

Log in

Denosumab versus bisphosphonates for the treatment of bone metastases from solid tumors: a systematic review

  • Original Paper
  • Published:
The European Journal of Health Economics Aims and scope Submit manuscript

Abstract

Background

Bone metastases are highly prevalent in breast, prostate, lung and colon cancers. Their symptoms negatively affect quality of life and functionality and optimal management can mitigate these problems. There are two different targeted agents to treat them: bisphosphonates (pamidronate and zoledronic acid) and the monoclonal antibody denosumab. Estimates of cost-effectiveness are still mixed.

Objective

To conduct a systematic review of economic studies that compares these two options.

Method

Literature search comprised eight databases and keywords for bone metastases, bisphosphonates, denosumab, and economic studies were used. Data were extracted regarding their methodologic characteristics and cost-effectiveness analyses. All studies were evaluated regarding to its methodological quality.

Results

A total of 263 unique studies were retrieved and six met inclusion criteria. All studies were based on clinical trials and other existing literature data, and they had high methodological quality. Most found unfavorable cost-effectiveness for denosumab compared with zoledronic acid, with adjusted ICERS that ranged from $4638–87,354 per SRE avoided and from US$57,274–4.81 M. per QALY gained, which varied widely according to type of tumor, time horizon, among others. Results were sensitive to drug costs, time to first skeletal-related event (SRE), time horizon, and utility.

Conclusions

Denosumab had unfavorable cost-effectiveness compared with zoledronic acid in most of the included studies. New economic studies based on real-world data and longer time horizons comparing these therapeutic options are needed.

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.

Fig. 1

(adapted from the PRISMA statement)

Similar content being viewed by others

References

  1. Aapro, M., Saad, F., Costa, L.: Optimizing clinical benefits of bisphosphonates in cancer patients with bone metastases. Oncologist 15, 1147–1158 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  2. Machado, M., Cruz, L.S., Tannus, G., Fonseca, M.: Efficacy of clodronate, pamidronate, and zoledronate in reducing morbidity and mortality in cancer patients with bone metastasis: a meta-analysis of randomized clinical trials. Clin. Ther. 31(5), 962–979 (2009)

    Article  CAS  PubMed  Google Scholar 

  3. Espinosa, J.C., Baamonde, A.G.A., Herrero, F.R., Martín, E.H.: SEOM guidelines for the treatment of bone metastases from solid tumours. Clin. Transl. Oncol. 14, 505–511 (2012)

    Article  CAS  Google Scholar 

  4. Choudhury, K.B., Mallik, C., Sharma, S., Choudhury, D.B., Maiti, S., Roy, C.: A randomized conrolled trial to compare the efficacy of bisphosphonates in the management of painful bone metastasis. Indian J. Palliat. Care 17(3), 210–218 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  5. Mundy, G.R.: Metastasis to bone: causes, consequences and therapeutic opportunities. Nature 2(8), 584–593 (2002)

    CAS  Google Scholar 

  6. Qian, Y., Song, X., Zhang, K., Balakumaran, A., Arellano, J.: Short-term disability in solid tumor patients with bone metastases and skeletal-related events. J. Med. Econ. 18(3), 210–218 (2015)

    Article  PubMed  Google Scholar 

  7. Husaini, H.A., Wheatley-Price, P., Clemons, M., Shepherd, F.A.: Prevention and management of bone metastases in lung cancer: a review. J. Thorac. Oncol. 4(2), 251–259 (2009)

    Article  PubMed  Google Scholar 

  8. Zustovich, F., Fabiani, F.: Therapeutic opportunities for castration-resistant prostate cancer patients with bone metastases. Crit. Rev. Oncol. Hematol. 91, 197–209 (2014)

    Article  PubMed  Google Scholar 

  9. Coleman, R.E.: Risks and benefits of bisphosphonates. Br. J. Cancer 98, 1736–1740 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Carter, J.A., Joshi, A.D., Kaura, S., Botteman, M.F.: Pharmacoeconomics of bisphosphonates for skeletal related event prevention in metastatic non-breast solid tumours. Pharmacoeconomics 30(5), 373–386 (2012)

    Article  PubMed  Google Scholar 

  11. Food and Drug Administration (FDA): Highlights of prescribing information: zometa (zoledronic acid). http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021223s028lbl.pdf (2014). Accessed 25 Jul 2016

  12. Coleman, R., Body, J.J., Aapro, M., Hadjii, P., Herretedt, J.: Bone health in cancer patients: ESMO clinical practice guidelines. Ann. Oncol. 25, 124–137 (2014)

    Article  Google Scholar 

  13. Steger, G.G., Bartsch, R.: Denosumab for the treatment of bone metastasis in breast cancer: evidence and opinion. Ther. Adv. Med. Oncol. 3(5), 233–243 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Food and Drug Administration (FDA): Highlights of prescribing information: xgeva (denosumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125320s094lbl.pdf (2013). Accessed 05 Jul 2017

  15. Guimarães, H.P., Barbosa, L.M., Laranjeira, L.N., Avezum, A.: Pharmacoeconomic evaluations and economical analyses: basic concepts. Rev. Bras. Hipertens. 14(4), 265–268 (2007)

    Google Scholar 

  16. Secoli, S.R., Padilha, K.G., Litvoc, J., Maeda, S.T.: Pharmacoeconomics: resultant perspective of decisions process. Cien. Saude. Colet. 10, 287–296 (2005)

    Article  Google Scholar 

  17. Goodwin, P.J.: Economic factors in cancer palliation—methodological considerations. Cancer Treat. Rev. 19, 59–65 (1993)

    Article  PubMed  Google Scholar 

  18. Bruner, D.W.: Cost-effectiveness and palliative care. Semin. Oncol. Nurs. 14(2), 164–167 (1998)

    Article  CAS  PubMed  Google Scholar 

  19. Greenberg, D., Earle, C., Fang, C., Eldar-Lissai, A., Neumann, P.J.: When is cancer care cost-effective? A systematic overview of cost-utility analysis in oncology. J. Natl. Cancer Inst. 102(2), 82–88 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  20. Santos, C.M.C., Pimenta, C.A.M., Nobre, M.R.C.: A estratégia PICO para construção da pergunta de pesquisa e busca de evidências. Rev. Latino-am. Enfermagem. 15(3), 508–511 (2007)

    Article  Google Scholar 

  21. Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G.: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann. Intern. Med. 151(4), 264–269 (2009)

    Article  PubMed  Google Scholar 

  22. Sanders, G.D., Neumann, P.J., Basu, A., Brock, D.W., Feeny, D., Krahn, M., et al.: Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine. JAMA 316(10), 1093–1103 (2016)

    Article  PubMed  Google Scholar 

  23. Joanna Briggs Institute: The Joanna Briggs Institute critical appraisal tools for use in JBI systematic reviews: checklist for economic evaluations. http://joannabriggs.org/research/critical-appraisal-tools.html (2016). Accessed 24 Jul 2017

  24. Phillips, B., Ball, C., Sackett, D., et al.: Oxford centre for evidence-based medicine levels of evidence grades of recommendation. http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009 (2009). Accessed 24 Jul 2017

  25. Arellano, J., Cristino, J., Chen, K.: Economic impact of denosumab for skeletal related event prevention in patients with prostate cancer and bone metastasis from a United States managed care organization perspective. Value Health 16(7), A398–A399 (2013)

    Article  Google Scholar 

  26. Chen, K., Arellano, J., Cristino, J.: Economic impact of denosumab for skeletal related event prevention in patients with breast cancer and bone metastasis from a United States managed care organization perspective. Value Health 16(7), A400 (2013)

    Article  Google Scholar 

  27. Rader, M.E., Danese, M., Conz, Z., Haplerin, M., Qian, Y., Goessl, C.D.: Lifetime cost effectiveness of denosumab versus zoledronic acid for prevention of skeletal-related events (SRE) in patients (pts) with castration-resistant prostate cancer (CRPC) and bone metastases (BM): United States managed care perspective. J. Clin. Oncol. 30(15), Suppl. 1 (2012)

    Google Scholar 

  28. Rader, M.E., Danese, M., Con, Z., Halperin, M., Qian, Y., Goessl, C.D., et al.: Cost-effectiveness of denosumab (Dmab) versus zoledronic acid (ZA) for the prevention of skeletal-related events (SREs) in patients (pts) with castrate-resistant prostate cancer (CRPC) and bone metastases (BM). J. Clin. Oncol. 30(5), Suppl. 1 (2012)

    Google Scholar 

  29. Chung, K., Rader, M.E., Danese, M., Cong, Z., Halperin, M., Qian, Y., et al.: Cost-effectiveness of denosumab versus zoledronic acid in the prevention of skeletal-related events (SREs) in patients with castration-resistant prostate cancer (CRPC) and bone metastases (BM). J. Oncol. Pharm. Pract. 18(Suppl1), 7–8 (2012)

    Google Scholar 

  30. Chung, K., Stopeck, A., Danese, M., Cong, Z., Halperin, M., Qian, Y., et al.: Cost-effectiveness of denosumab versus zoledronic acid in the prevention of skeletal-related events (SREs) in patients with breast cancer and bone metastases (BM). J. Oncol. Pharm. Pract. 18(Suppl1), 6–7 (2012)

    Google Scholar 

  31. Northridge, K., Richhariya, K., Halperin, M., Ghung, K., Danese, M.D.: Budget impact model of denosumab for skeletal-related event (SRE) prevention in patients with breast and prostate cancer. Value Health 4(3), A159 (2011)

    Article  Google Scholar 

  32. Bell, M.J., Miller, J.D., Namjoshi, M., Russel, M.W.: Comparative budget impact of formulary inclusion of zoledronic acid and denosumab for prevention of skeletal-related events in patients with bone metastases. Value Health 4(3), A153 (2011)

    Google Scholar 

  33. Yu, A.P., Namjoshi, M.P., Xie, J., Parikh, K., Wu, E.Q., Guo, A., et al.: Economic evaluation of denosumab compared with zoledronic acid in patients with hormone refractory prostate cancer with bone metastases. J. Clin. Oncol. 29(15), Suppl. 1 (2011)

    Google Scholar 

  34. Russell, M.W., Bell, M.J., Namjoshi, M., Miller, J.D.: Financial impact of coverage for zoledronic acid and denosumab for prevention of skeletal-related events in cancer patients with bone metastases. J Clin Oncol. 29(15), Suppl. 1 (2011)

    Article  Google Scholar 

  35. Arocho, R., Rivera Hurtado, R., Carlos, F.: Economic evaluation of denosumab versus zoledronic acid (ZA) in the prevention of skeletal-related events (SRE) in patients with prostate cancer with bone metastasis (BM) in Mexico. Value Health 16(3), A139–A140 (2013)

    Article  Google Scholar 

  36. Alva, M.E., Naranjo, M., Zamora, J.: Economic evaluation of denosumab in the prevention of SRE in patients with breast cancer in Mexico. Value Health 19(3), A151–A152 (2016)

    Article  Google Scholar 

  37. Duran, I., Seguí, M.A., Isla, D., Oyagüez, I., Roldán, C., Casado, M.A.: Cost-effectiveness of denosumab versus zoledronic acid in patients with bone metastases from solid tumors in Spain. Eur. J. Cancer 49(Suppl2), A334 (2013)

    Google Scholar 

  38. Lothgren, M., Bracco, A., Lucius, B., Northridge, K., Halperin, M., Macarios, D., et al.: Cost-effectiveness of denosumab versus zoledronic acid (ZA) for the prevention of skeletal-related events (SRE) in patients with bone metastases from solid tumors in the Netherlands. Value Health 14(7), A455 (2011)

    Article  Google Scholar 

  39. Bektur, C., Nurgozhin, T.: Cost-effectiveness of denosumab vs. brand or generic zoledronic acid in patients with breast cancer in Kazakhstan. Value Health 17(7), A773 (2014)

    PubMed  Google Scholar 

  40. Koo, K., Lam, K., Mittmann, N., Konski, A., Dennis, K., Zeng, L.: Comparing cost-effectiveness analyses of denosumab versus zoledronic acid for the treatment of bone metastases. Support. Care Cancer 21(6), 1785–1791 (2013)

    Article  PubMed  Google Scholar 

  41. Carter, J.A., Botteman, M.F.: Health-economic review of zoledronic acid for the management of skeletal-related events in bone-metastatic prostate cancer. Exp. Rev. Pharmacoecon. Outcomes Res. 12(4), 425–437 (2012)

    Article  Google Scholar 

  42. Dellis, A., Papatsoris, A.: Cost-effectiveness of denosumab as a bone protective agent for patients with castration resistant prostate cancer. Exp. Rev. Pharmacoecon. Outcomes. Res. 16(1), 5–10 (2016)

    Article  Google Scholar 

  43. Ford, J., Cummins, E., Sharma, P., Elders, A., Stewart, F., Johnston, R., et al.: Systematic review of the clinical effectiveness and cost-effectiveness, and economic evaluation, of denosumab for the treatment of bone metastases from solid tumours. Heath Technol. Assess. 17(29), 1–386 (2013)

    CAS  Google Scholar 

  44. Xie, J., Namjoshi, M., Wu, E.Q., Parikh, K., Diener, M., Yu, A.P.: Economic evaluation of debosumab compared with zoledronic acid in hormone refractory prostate cancer patients with bone metastases. J. Manag. Care Pharm. 17(8), 621–634 (2011)

    PubMed  Google Scholar 

  45. Xie, J., Diener, M., Sorg, R., Wu, E.Q., Namjoshi, M.: Cost-effectiveness of denosumab compared with zoledronic acid in patients with breast cancer and bone metastases. Clin. Breast Cancer 12(4), 247–258 (2012)

    Article  PubMed  Google Scholar 

  46. Snedecor, S.J., Carter, J.A., Kaura, S., Botteman, M.F.: Cost-effectiveness of denosumab versus zoledronic acid in the management of skeletal metastases secondary to breast cancer. Clin. Ther. 34(6), 1334–1349 (2012)

    Article  PubMed  Google Scholar 

  47. Stopeck, A., Rader, M., Henry, D., Danese, M., Halperin, M., Cong, Z., et al.: cost-effectiveness of denosumab versus zoledronic acid for prevention of skeletal-related events in patients with solid tumors and bone metastases in the united states. J. Med. Econ. 15(4), 712–723 (2012)

    Article  PubMed  Google Scholar 

  48. Snedecor, S.J., Carter, J.A., Kaura, S., Botteman, M.F.: Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a cost-effectiveness analysis. J. Med. Econ. 16(1), 19–29 (2013)

    Article  PubMed  Google Scholar 

  49. Yfantopoulos, J., Christopoulou, A., Chatzikou, M., Fishman, P., Chalzaras, A.: The importance of economic evaluation in healthcare decision making—a case of denosumab versus zoledronic acid from Greece. A third-payer perspective. Forum Clin. Oncol. 4(2), 25–31 (2013)

    Google Scholar 

  50. Haas, J.S., Moskowitz, E.J.: Health technology assessment in canada and the United States: the case of biologics. Biotechnol. Health 4(2), 47–51 (2007)

    Google Scholar 

  51. Menon, D., Stafinski, T.: Health technology assessment in Canada: 20 years strong? Value Health 12(2), S14–S19 (2009)

    Article  PubMed  Google Scholar 

  52. Novaes, M.H.D., Elias, F.T.S.: Use of health technology assessment in decision-making processes by the Brazilian Ministry of Health on the incorporation of technologies in the Brazilian Unified National Health System. Cad. Saude Pública 29, S7–S16 (2013)

    Article  PubMed  Google Scholar 

  53. Novaes, M.H.D., Soárez, P.C.: Health technology assessment (HTA) organizations: dimensions of the institutional and political framework. Cad. Saúde Pública 32, S1–S14 (2016)

    Article  Google Scholar 

  54. Carter, J.A., Snedecor, S.J., Kaura, S.: Cost effectiveness of zoledronic acid (ZOL) versus denosumab (Dmab) in prevention of skeletal related events (SREs) in metastatic breast cancer (mBC). J. Clin. Oncol. 29(suppl), abstract 9025 (2011)

    Article  Google Scholar 

  55. Henry, D., Vadhan-Raj, S., Hirsh, V., von Moos, R., Hungria, V., Costa, C.: Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data from patients with solid tumors. Support. Care Cancer 22, 679–687 (2014)

    Article  PubMed  Google Scholar 

  56. Andronis, L., Goranitis, I., Bayliss, S., Duarte, R.: Cost-effectiveness of treatments for the management of bone metastases: a systematic literature review. PharmacoEconomics 36, 301–322 (2018)

    Article  PubMed  Google Scholar 

  57. Garattini, L., van de Vooren, K.: Budget impact analysis in economic evaluation: a proposal for a clearer definition. Eur. J. Health Econ. 12, 499–502 (2011)

    Article  PubMed  Google Scholar 

  58. Lexchin, J., Bero, L.A., Djulbegovic, B., Clark, O.: Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ 326, 1167–1170 (2003)

    Article  PubMed  PubMed Central  Google Scholar 

  59. Schott, G., Pachl, H., Limbach, U., Gundert-Remy, U., Ludwig, W.D., Lieb, K.: The financing of drug trials by pharmaceutical companies and its consequences. Dtsch. Arztebl. Int. 107(16), 279–285 (2010)

    PubMed  PubMed Central  Google Scholar 

  60. Neumann, P.J., Cohen, J.T., Weinstein, P.C.: Updating cost-effectiveness—the curious resilience of the $50,000-per-QALY threshold. N. Engl. J. Med. 371(9), 796–797 (2014)

    Article  CAS  PubMed  Google Scholar 

  61. Rascati, K.L.: Criticando Artigos de Pesquisa. In: Rascati, K.L. (ed.) Introducão à Farmacoeconomia, pp. 45–54. Artmed, Porto Alegre (2010)

    Google Scholar 

  62. Cohen, D.J., Reynolds, M.R.: Interpreting the results of cost-effectiveness studies. J. Am. Coll. Cardiol. 52(25), 2119–2126 (2008)

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jessica Y. Matuoka.

Ethics declarations

Human/animal rights statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors have no conflicts of interest to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matuoka, J.Y., Kahn, J.G. & Secoli, S.R. Denosumab versus bisphosphonates for the treatment of bone metastases from solid tumors: a systematic review. Eur J Health Econ 20, 487–499 (2019). https://doi.org/10.1007/s10198-018-1011-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10198-018-1011-1

Keywords

JEL

Navigation