Denosumab in men receiving androgen-deprivation therapy for prostate cancer.

Full Abstract

BACKGROUND: Androgen-deprivation therapy is well-established for treating prostate cancer but is associated with bone loss and an increased risk of fracture. We investigated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. METHODS: In this double-blind, multicenter study, we randomly assigned patients to receive denosumab at a dose of 60 mg subcutaneously every 6 months or placebo (734 patients in each group). The primary end point was percent change in bone mineral density at the lumbar spine at 24 months. Key secondary end points included percent change in bone mineral densities at the femoral neck and total hip at 24 months and at all three sites at 36 months, as well as incidence of new vertebral fractures. RESULTS: At 24 months, bone mineral density of the lumbar spine had increased by 5.6% in the denosumab group as compared with a loss of 1.0% in the placebo group (P<0.001); significant differences between the two groups were seen at as early as 1 month and sustained through 36 months. Denosumab therapy was also associated with significant increases in bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. Patients who received denosumab had a decreased incidence of new vertebral fractures at 36 months (1.5%, vs. 3.9% with placebo) (relative risk, 0.38; 95% confidence interval, 0.19 to 0.78; P=0.006). Rates of adverse events were similar between the two groups. CONCLUSIONS: Denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. (ClinicalTrials.gov number, NCT00089674.) 2009 Massachusetts Medical Society

Author information

Author/s: Smith, Matthew R (MR); Egerdie, Blair (B); Hernández Toriz, Narciso (N); Feldman, Robert (R); Tammela, Teuvo L J (TL); Saad, Fred (F); Heracek, Jiri (J); Szwedowski, Maciej (M); Ke, Chunlei (C); Kupic, Amy (A); Leder, Benjamin Z (BZ); Goessl, Carsten (C); Denosumab HALT Prostate Cancer Study Group;

Affiliation: Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. smith.matthew(-atsign-)mgh.harvard.edu

Grants: 5K24CA121990-02 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The New England journal of medicine (N Engl J Med), published in United States. (Language: eng)

Reference: 2009-Aug; vol 361 (issue 8) : pp 745-55

Dates: Created 2009/08/20; Completed 2009/08/27;

PMID: 19671656, status: MEDLINE (last retrieved date: 8/27/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: N Engl J Med. 2009 Aug 20;361(8):818-20. (PMID: 19671654)

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Aged
Aged, 80 and over
Androgen Antagonists - adverse effects; therapeutic use
Antibodies, Monoclonal - adverse effects; pharmacology; therapeutic use
Bone Density - drug effects
Bone Density Conservation Agents - adverse effects; pharmacology; therapeutic use
Bone Remodeling - drug effects
Double-Blind Method
Fractures, Bone - epidemiology; prevention & control
Gonadotropin-Releasing Hormone - agonists
Humans

Humans
Incidence
Injections, Subcutaneous
Lumbar Vertebrae - drug effects; injuries; physiology
Male
Middle Aged
Orchiectomy
Osteoporosis - chemically induced; drug therapy
Prostatic Neoplasms - drug therapy; physiopathology; surgery
RANK Ligand - adverse effects; pharmacology; therapeutic use
Spinal Fractures - epidemiology; prevention & control

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Androgen Antagonists (0) ; Antibodies, Monoclonal (0) ; Bone Density Conservation Agents (0) ; RANK Ligand (0) ; Gonadotropin-Releasing Hormone (33515-09-2) ; denosumab (615258-40-7)

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