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Original article

Vol. 151 No. 0910 (2021)

Patterns of care and economic consequences of using bone-targeted agents for castration-sensitive prostate cancer patients with bone metastases to prevent skeletal-related events in Switzerland – the SAKK 95/16 prostate study

DOI
https://doi.org/10.4414/smw.2021.20464
Cite this as:
Swiss Med Wkly. 2021;151:w20464
Published
01.03.2021

Summary

BACKGROUND

International guidelines state that bone-targeted agents such as denosumab or zoledronic acid at doses used for bone metastasis are not indicated for patients with metastatic castration-sensitive prostate cancer (mCSPC) with bone metastases. Whereas denosumab has never been studied in this patient population, zoledronic acid has been shown to be ineffective in decreasing the risk for skeletal-related events. This study estimates the prevalence and economic consequences of real-world use of bone-targeted agents for mCSPC patients in Switzerland.

METHODS

To estimate the frequency of bone-targeted agent administration and skeletal-related events, data from a non-interventional, cross-sectional survey involving oncologists across Switzerland (SAKK 95/16) was combined with data from the Swiss National Institute for Cancer Epidemiology and Registration (NICER). Economic parameters were calculated from the perspective of the healthcare system over the median time to prostate-specific antigen (PSA) progression for the extrapolated patient group, using data from NICER. The cost calculation covered costs for bone-targeted agents, their administration and skeletal-related events. The time to PSA progression (33.2 months), as well as the probability and cost of skeletal-related events were derived from the literature.

RESULTS

The survey was answered by 86 physicians treating 417 patients, of whom 106 (25.4%) had prostate cancer, with 36 (34.0%) of these mCSPC. The majority of mCSPC patients (52.8%, n = 19) received bone-targeted agents monthly. Denosumab was the treatment of choice in 84.2% of patients (n = 16). Extrapolation using data from NICER indicated that 568 mCSPC patients may be treated with bone-targeted agents at doses used for bone metastasis every year in Switzerland, leading to estimated total costs of more than CHF 8.3 million over 33.2 months. Because of its more frequent prescription and higher price, it appears that almost 93% of the total costs can be attributed to denosumab. For both denosumab and zoledronic acid, the most expensive components were the cost of administration and the drug cost, making up more than 90% of the total costs, with the rest being costs of skeletal-related events.

CONCLUSIONS

This study found that the administration of bone-targeted agents in doses used for bone-metastatic diseases to prevent skeletal-related events is frequent in the setting of mCSPC and results in significant costs for the healthcare system.

References

  1. So A, Chin J, Fleshner N, Saad F. Management of skeletal-related events in patients with advanced prostate cancer and bone metastases: Incorporating new agents into clinical practice. Can Urol Assoc J. 2012;6(6):465–70. doi:.https://doi.org/10.5489/cuaj.117
  2. Weinfurt KP, Li Y, Castel LD, Saad F, Timbie JW, Glendenning GA, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol. 2005;16(4):579–84. doi:.https://doi.org/10.1093/annonc/mdi122
  3. Wang Z, Qiao D, Lu Y, Curtis D, Wen X, Yao Y, et al. Systematic literature review and network meta-analysis comparing bone-targeted agents for the prevention of skeletal-related events in cancer patients with bone metastasis. Oncologist. 2015;20(4):440–9. doi:.https://doi.org/10.1634/theoncologist.2014-0328
  4. Yee AJ, Raje NS. Denosumab, a RANK ligand inhibitor, for the management of bone loss in cancer patients. Clin Interv Aging. 2012;7:331–8.
  5. Smith MR, Saad F, Egerdie B, Szwedowski M, Tammela TL, Ke C, et al. Effects of denosumab on bone mineral density in men receiving androgen deprivation therapy for prostate cancer. J Urol. 2009;182(6):2670–6. doi:.https://doi.org/10.1016/j.juro.2009.08.048
  6. Body JJ. Denosumab for the management of bone disease in patients with solid tumors. Expert Rev Anticancer Ther. 2012;12(3):307–22. doi:.https://doi.org/10.1586/era.11.204
  7. Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377(9768):813–22. doi:.https://doi.org/10.1016/S0140-6736(10)62344-6
  8. Parker C, Castro E, Fizazi K, Heidenreich A, Ost P, Procopio G, et al.; ESMO Guidelines Committee. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(9):1119–34. doi:.https://doi.org/10.1016/j.annonc.2020.06.011
  9. Hegemann M, Bedke J, Stenzl A, Todenhöfer T. Denosumab treatment in the management of patients with advanced prostate cancer: clinical evidence and experience. Ther Adv Urol. 2017;9(3-4):81–8. doi:.https://doi.org/10.1177/1756287216686018
  10. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, et al.; STAMPEDE investigators. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163–77. doi:.https://doi.org/10.1016/S0140-6736(15)01037-5
  11. Smith MR, Halabi S, Ryan CJ, Hussain A, Vogelzang N, Stadler W, et al. Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance). J Clin Oncol. 2014;32(11):1143–50. doi:.https://doi.org/10.1200/JCO.2013.51.6500
  12. Saylor PJ, Rumble RB, Tagawa S, Eastham JA, Finelli A, Reddy PS, et al. Bone Health and Bone-Targeted Therapies for Prostate Cancer: ASCO Endorsement of a Cancer Care Ontario Guideline. J Clin Oncol. 2020;38(15):1736–43. doi:.https://doi.org/10.1200/JCO.19.03148
  13. Horwich A, Hugosson J, de Reijke T, Wiegel T, Fizazi K, Kataja V, et al.; Panel Members; European Society for Medical Oncology. Prostate cancer: ESMO Consensus Conference Guidelines 2012. Ann Oncol. 2013;24(5):1141–62. doi:.https://doi.org/10.1093/annonc/mds624
  14. Swissmedic Journal. 12/2011. Available at: https://www.swissmedic.ch/dam/swissmedic/de/dokumente/stab/journal/swissmedic_journal122011.pdf.download.pdf/swissmedic_journal122011.pdf [cited 2020 June 15]
  15. European Medicines Agency. Xgeva (denosumab) summary of product characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/xgeva-epar-product-information_en.pdf [cited 2020 September 2]
  16. Swissmedic Journal. 2/2012. Available at: https://www.swissmedic.ch/dam/swissmedic/de/dokumente/stab/journal/swissmedic_journal022012.pdf.download.pdf/swissmedic_journal022012.pdf [cited 2020 June 15]
  17. European Medicines Agency. Zometa (zoledronic acid) summary of product characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/zometa-epar-product-information_en.pdf [cited 2020 September 2].
  18. Hofmarcher T, Lindgren P, Wilking N, Jönsson B. The cost of cancer in Europe 2018. Eur J Cancer. 2020;129:41–9. doi:.https://doi.org/10.1016/j.ejca.2020.01.011
  19. Mark M, Thürlimann B, Ribi K, Schär C, Dietrich D, Cathomas R, et al. Patterns of care for patients with metastatic bone disease in solid tumors: A cross-sectional study from Switzerland (SAKK 95/16). J Bone Oncol. 2020;21:100273. doi:.https://doi.org/10.1016/j.jbo.2019.100273
  20. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281(17):1591–7. doi:.https://doi.org/10.1001/jama.281.17.1591
  21. Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000;31(5):578–83. doi:.https://doi.org/10.1053/hp.2000.6698
  22. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al.; LATITUDE Investigators. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377(4):352–60. doi:.https://doi.org/10.1056/NEJMoa1704174
  23. Tarmed Suisse Online browser. Tarmed list 2020. Available at: https://www.tarmed-browser.ch [cited 2020 July 14]
  24. Swiss Federal Office of Public Health. Specialty List 2019; https://www.spezialitätenliste.ch/ [cited 2020 June 15]
  25. Fizazi K, Brown JE, Carducci M, Shore ND, Sieber P, Kueppers F, et al. Denosumab in patients with metastatic prostate cancer previously treated with denosumab or zoledronic acid: 2-year open-label extension phase results from the pivotal phase 3 study. Ann Oncol. 2012;23:ix309. doi:.https://doi.org/10.1016/S0923-7534(20)33497-9
  26. Najm MS, Solomon DH, Woo SB, Treister NS. Resource utilization in cancer patients with bisphosphonate-associated osteonecrosis of the jaw. Oral Dis. 2014;20(1):94–9. doi:.https://doi.org/10.1111/odi.12080
  27. US Bureau Of Labor Statistics. CPI Inflation calculator. Available at: https://www.bls.gov/data/inflation_calculator.htm [cited 2020 July 10]
  28. Organisation for Economic Co-operation and Development. Purchasing power parities (PPP). Available at: https://data.oecd.org/conversion/purchasing-power-parities-ppp.htm [cited 2020 September 14]
  29. Rothermund C, Gillessen S, Cerny T. Zulassung Denosumab (XGEVA). Received by Schnetzer J, 2012 June 17.
  30. Yee AJ, Raje NS. Denosumab, a RANK ligand inhibitor, for the management of bone loss in cancer patients. Clin Interv Aging. 2012;7:331–8. doi:.https://doi.org/10.2147/CIA.S14566
  31. Miksad RA, Lai KC, Dodson TB, Woo SB, Treister NS, Akinyemi O, et al. Quality of life implications of bisphosphonate-associated osteonecrosis of the jaw. Oncologist. 2011;16(1):121–32. doi:.https://doi.org/10.1634/theoncologist.2010-0183
  32. Nicolatou-Galitis O, Schiødt M, Mendes RA, Ripamonti C, Hope S, Drudge-Coates L, et al. Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019;127(2):117–35. doi:.https://doi.org/10.1016/j.oooo.2018.09.008
  33. Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al.; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381(2):121–31. doi:.https://doi.org/10.1056/NEJMoa1903835
  34. Antonarakis ES, Feng Z, Trock BJ, Humphreys EB, Carducci MA, Partin AW, et al. The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up. BJU Int. 2012;109(1):32–9. doi:.https://doi.org/10.1111/j.1464-410X.2011.10422.x
  35. Moul JW, Wu H, Sun L, McLeod DG, Amling C, Lance R, et al. Epidemiology of radical prostatectomy for localized prostate cancer in the era of prostate-specific antigen: an overview of the Department of Defense Center for Prostate Disease Research national database. Surgery. 2002;132(2):213–9. doi:.https://doi.org/10.1067/msy.2002.125315

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