What are the indications for starting denosumab (Prolia/Xgeva)?

From the Guidelines

Denosumab is indicated for patients with castration-resistant prostate cancer (CRPC) and bone metastases to prevent or delay disease-associated skeletal-related events (SREs). The use of denosumab in these patients is supported by the results of a randomized, double-blind, placebo-controlled study, which showed that denosumab delayed the median time to SRE by 3.6 months compared with zoledronic acid 1. The recommended dose of denosumab for this indication is 120 mg subcutaneously every 4 weeks.

Some key points to consider when using denosumab in patients with CRPC and bone metastases include:

• Dental evaluation is recommended before initiation due to the risk of osteonecrosis of the jaw 1
• Patients should have their calcium and vitamin D levels assessed and corrected if deficient before starting denosumab 1
• Denosumab works by inhibiting RANK ligand, which prevents osteoclast formation and activation, thereby reducing bone resorption and increasing bone density 1
• Unlike bisphosphonates, denosumab is not renally cleared, making it suitable for patients with kidney disease 1
• However, patients should be aware that discontinuation leads to rapid bone loss, so transition to another therapy is typically needed when stopping treatment 1

It's also important to note that denosumab has been compared with zoledronic acid in patients with CRPC and bone metastases, and the results showed that denosumab was superior to zoledronic acid in delaying the time to first SRE 1. Additionally, denosumab has been shown to be effective in reducing the risk of multiple SREs in patients with advanced solid tumors and multiple myeloma 1.

Overall, denosumab is a valuable treatment option for patients with CRPC and bone metastases, and its use should be considered in the context of a comprehensive treatment plan that includes dental evaluation, calcium and vitamin D supplementation, and monitoring for potential adverse events.

From the FDA Drug Label

Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy Prolia is indicated for treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy Prolia is indicated for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk of fracture who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and expected to remain on glucocorticoids for at least 6 months Prolia is indicated as a treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy (ADT) for nonmetastatic prostate cancer Prolia is indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

The indications for starting denosumab are:

• Postmenopausal women with osteoporosis at high risk for fracture
• Men with osteoporosis at high risk for fracture
• Glucocorticoid-induced osteoporosis in men and women at high risk of fracture
• Men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer 2 2

From the Research

Indications for Starting Denosumab

Denosumab is indicated for use in various conditions, including:

• Osteoporosis in postmenopausal women and men, to improve bone mineral density and reduce the incidence of new vertebral, hip, and nonvertebral fractures 3, 4, 5
• Prevention of bone loss and reduction of fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer 3, 4, 5
• Prevention of bone loss and reduction of fracture risk in women receiving adjuvant aromatase inhibitor therapy for breast cancer 5
• Treatment of glucocorticoid-induced osteoporosis 5

Patient Selection

Denosumab may be used as initial therapy in patients at high risk for fracture, including:

• Older patients who have difficulty with the dosing requirements of oral bisphosphonates 3, 5
• Patients who are intolerant of, unresponsive to, or have contraindications to other therapies 3, 5
• Patients with impaired renal function 3

Important Considerations

Before starting denosumab, it is essential to consider the following:

• Risk of hypocalcemia, particularly in patients with diffuse metastatic bone disease or pre-existing low levels of calcium 6, 7
• Importance of early supplementation with calcium and vitamin D to prevent or mitigate hypocalcemia 6, 7
• Potential risk factors for hypocalcemia, including age ≥65 years, grade 1 or higher serum alkaline phosphatase elevation, adjusted serum calcium level of less than 9.3 mg/dL at baseline, and co-administration of cytotoxic agents 7