Denosumab Treatment in the Management of Patients with Advanced Prostate Cancer: Clinical Evidence and Experience

Overview

Journal Ther Adv Urol

Publisher Sage Publications

Date 2017 Apr 11

PMID 28392837

Citations 19

Authors

Miriam Hegemann

Jens Bedke

Arnulf Stenzl

Tilman Todenhofer

Affiliations

Soon will be listed here.

Abstract

Osteoprotective therapies have become an essential component in the management of advanced prostate cancer (PC) patients as bone metastases (BMs) have a major impact on morbidity and mortality. Denosumab is a fully humanized antibody targeting the receptor activator of nuclear factor κB ligand (RANKL), which has been approved by the European Medicines Agency (EMA) in Europe and the United States (US) Food and Drug Administration (FDA) in the US for prevention of skeletal-related events (SREs) in patients with solid tumors and BMs, including PC. The clinical settings in which PC patients should be treated with denosumab are still discussed controversially. In a phase III study, denosumab significantly delayed SREs compared with zoledronic acid (ZA) in patients with metastatic castration-resistant PC (CRPC). In addition, denosumab showed superior effects on pain and health-related quality of life (QoL) in these patients. In patients with nonmetastatic CRPC, denosumab has been proven to significantly increase bone metastases-free survival. However, no significant benefits on cancer-specific and overall survival were observed and denosumab was not approved by the US FDA and EMA in this context. The effectiveness of denosumab in patients with castration-sensitive PC (CSPC) and BMs is also under discussion, as clinical trials with ZA in these patients have not shown significant benefits. Clinical data on the use of denosumab in CSPC are urgently needed.

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References

Pound C, Partin A, Eisenberger M, Chan D, Pearson J, Walsh P . Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999; 281(17):1591-7. DOI: 10.1001/jama.281.17.1591. View

Bubendorf L, Schopfer A, Wagner U, Sauter G, Moch H, Willi N . Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000; 31(5):578-83. DOI: 10.1053/hp.2000.6698. View

Saad F, Gleason D, Murray R, Tchekmedyian S, Venner P, Lacombe L . A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst. 2002; 94(19):1458-68. DOI: 10.1093/jnci/94.19.1458. View

Boyle W, Simonet W, Lacey D . Osteoclast differentiation and activation. Nature. 2003; 423(6937):337-42. DOI: 10.1038/nature01658. View

Prentice A . Diet, nutrition and the prevention of osteoporosis. Public Health Nutr. 2004; 7(1A):227-43. DOI: 10.1079/phn2003590. View

Saad F, Gleason D, Murray R, Tchekmedyian S, Venner P, Lacombe L . Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst. 2004; 96(11):879-82. DOI: 10.1093/jnci/djh141. View

Shahinian V, Kuo Y, Freeman J, Goodwin J . Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2005; 352(2):154-64. DOI: 10.1056/NEJMoa041943. View

Weinfurt K, Li Y, Castel L, Saad F, Timbie J, Glendenning G . 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: 10.1093/annonc/mdi122. View

Hess K, Varadhachary G, Taylor S, Wei W, Raber M, Lenzi R . Metastatic patterns in adenocarcinoma. Cancer. 2006; 106(7):1624-33. DOI: 10.1002/cncr.21778. View

10.

Lipton A, Cook R, Saad F, Major P, Garnero P, Terpos E . Normalization of bone markers is associated with improved survival in patients with bone metastases from solid tumors and elevated bone resorption receiving zoledronic acid. Cancer. 2008; 113(1):193-201. DOI: 10.1002/cncr.23529. View

11.

Aragon-Ching J, Ning Y, Chen C, Latham L, Guadagnini J, Gulley J . Higher incidence of Osteonecrosis of the Jaw (ONJ) in patients with metastatic castration resistant prostate cancer treated with anti-angiogenic agents. Cancer Invest. 2009; 27(2):221-6. PMC: 2648132. DOI: 10.1080/07357900802208608. View

12.

Fizazi K, Lipton A, Mariette X, Body J, Rahim Y, Gralow J . Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol. 2009; 27(10):1564-71. DOI: 10.1200/JCO.2008.19.2146. View

13.

Smith M, Egerdie B, Toriz N, Feldman R, Tammela T, Saad F . Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009; 361(8):745-55. PMC: 3038121. DOI: 10.1056/NEJMoa0809003. View

14.

Ibrahim T, Flamini E, Mercatali L, Sacanna E, Serra P, Amadori D . Pathogenesis of osteoblastic bone metastases from prostate cancer. Cancer. 2010; 116(6):1406-18. DOI: 10.1002/cncr.24896. View

15.

Norgaard M, Jensen A, Jacobsen J, Cetin K, Fryzek J, Sorensen H . Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007). J Urol. 2010; 184(1):162-7. DOI: 10.1016/j.juro.2010.03.034. View

16.

Stopeck A, Lipton A, Body J, Steger G, Tonkin K, De Boer R . Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010; 28(35):5132-9. DOI: 10.1200/JCO.2010.29.7101. View

17.

Henry D, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J . Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011; 29(9):1125-32. DOI: 10.1200/JCO.2010.31.3304. View

18.

Fizazi K, Carducci M, Smith M, Damiao R, Brown J, Karsh L . 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. PMC: 3090685. DOI: 10.1016/S0140-6736(10)62344-6. View

19.

Sullivan S, Wagner J, Resnick N, Nelson J, Perera S, Greenspan S . Vertebral fractures and the misclassification of osteoporosis in men with prostate cancer. J Clin Densitom. 2011; 14(3):348-53. PMC: 3150288. DOI: 10.1016/j.jocd.2011.05.003. View

20.

Dhanapal V, Reeves D . Bone health management in prostate cancer patients receiving androgen deprivation therapy. J Oncol Pharm Pract. 2011; 18(1):84-90. DOI: 10.1177/1078155211402105. View