What is the use of Denosumab (Prolia, Xgeva)?

From the Guidelines

Denosumab (Prolia, Xgeva) is used to prevent or delay skeletal-related events (SREs) in patients with bone metastases from cancer, particularly in those with castration-resistant prostate cancer (CRPC) and breast cancer.

Key Uses of Denosumab

• Prevention or delay of SREs, such as pathologic fractures, spinal cord compression, and need for radiation or surgery to bone, in patients with bone metastases from cancer
• Treatment of patients with CRPC and bone metastases to prevent or delay disease-associated SREs
• May be used in patients with impaired renal function or on hemodialysis, but with caution and close monitoring of serum calcium levels

Dosage and Administration

• Denosumab is administered subcutaneously every 4 weeks
• The recommended dose is 120 mg, with additional 120 mg doses on days 8 and 15 of the first month of treatment

Comparison with Zoledronic Acid

• Denosumab has been shown to be superior to zoledronic acid in preventing SREs in patients with bone metastases from CRPC and breast cancer 1
• Denosumab may have a more favorable safety profile than zoledronic acid, with a lower risk of renal toxicity and hypocalcemia 1

Important Safety Considerations

• Hypocalcemia is a common adverse event associated with denosumab, and patients should be monitored closely for signs and symptoms of hypocalcemia
• Osteonecrosis of the jaw (ONJ) is a rare but serious adverse event associated with denosumab, and patients should undergo a baseline dental evaluation and regular monitoring of oral conditions to detect early ONJ 1

Clinical Evidence

• Multiple studies have demonstrated the efficacy and safety of denosumab in preventing or delaying SREs in patients with bone metastases from cancer, including a phase III trial that showed denosumab to be superior to zoledronic acid in preventing SREs in patients with CRPC and bone metastases 1

From the FDA Drug Label

Prolia is a prescription medicine used to: Treat osteoporosis (thinning and weakening of bone) in women after menopause ("change of life") who:

• are at high risk for fracture (broken bone)
• cannot use another osteoporosis medicine or other osteoporosis medicines did not work well Increase bone mass in men with osteoporosis who are at high risk for fracture Treat osteoporosis in men and women who will be taking corticosteroid medicines (such as prednisone) for at least 6 months and are at high risk for fracture. Treat bone loss in men who are at high risk for fracture receiving certain treatments for prostate cancer that has not spread to other parts of the body Treat bone loss in women who are at high risk for fracture receiving certain treatments for breast cancer that has not spread to other parts of the body.

The use of Denosumab (Prolia, Xgeva) is to treat osteoporosis and increase bone mass in men and women at high risk for fracture, as well as to treat bone loss in men and women receiving certain treatments for prostate or breast cancer. 2

From the Research

Uses of Denosumab

• Denosumab (Prolia, Xgeva) is a fully human monoclonal antibody used in the treatment of osteoporosis, particularly in postmenopausal women and men at high risk of fracture 3, 4, 5.
• It is also used to prevent bone loss and reduce fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer 5.
• Denosumab has been shown to improve bone mineral density and reduce the incidence of new fractures in patients with osteoporosis 3, 4, 5.
• It is used in the treatment of glucocorticoid-induced osteoporosis and has been administered off-label in selected patients with rare metabolic bone diseases, such as Juvenile Paget disease, fibrous dysplasia, and Hajdu Cheney syndrome 6.

Administration and Safety

• Denosumab is administered via subcutaneous injection once every 6 months 4 or every 3 months in some cases 7.
• The drug has been shown to be generally well-tolerated, with a favorable benefit/risk profile 3, 4, 5.
• However, there is a potential risk of multiple vertebral fractures after discontinuation of denosumab, and transitioning to another anti-osteoporosis therapy after denosumab discontinuation is essential to mitigate this risk 3, 4, 5.
• Denosumab has also been associated with a low risk of osteonecrosis of the jaw and atypical femoral fracture 3, 4, 5.

Specific Uses

• Denosumab has been used in the treatment of breast cancer bone metastases, where it has been shown to delay and prevent skeletal-related events (SREs) 7.
• It has also been used off-label in patients with Paget's disease, osteogenesis imperfecta, and aneurysmal bone cysts, due to contraindications or unresponsiveness to standard treatment 6.