Xgeva – Denosumab
Patient Education Quick Reference Guide
Diablo Valley Oncology/Hematology Medical Group
Phone Number: 925-677-5041
Indications for Use
Denosumab is a receptor activator of nuclear factor-?B ligand (RANKL) inhibitor, indicated for the prevention of skeletal-related events (SRE) in patients with bone metastases from solid tumors. It is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.
Mechanism of Action
Denosumab is a fully human monoclonal antibody against RANKL. RANK is a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts. Osteoclasts are responsible for bone resorption. Denosumab prevents the binding of RANKL to RANK, effectively shutting down osteoclast-mediated bone resorption. Denosumab is the first FDA approved RANKL inhibitor.
The most common adverse reactions (?25%) reported in patients receiving denosumab were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction reported in patients receiving denosumab was dyspnea. The most common adverse reactions resulting in discontinuation of denosumab were osteonecrosis and hypocalcemia.
Denosumab can exacerbate hypocalcemia and patients predisposed to hypocalcemia and disturbances of mineral metabolism should be monitored for calcium and mineral (phosphorus and magnesium) levels. Patients with severe renal impairment (CrCl< 30 mg/min) or on renal dialysis are at significant risk for hypocalcemia and should be strictly monitored and encouraged to take adequate calcium and vitamin D supplements.
Osteonecrosis of the Jaw (ONJ)
ONJ has been reported with denosumab use and it is important for patients to undergo a routine oral exam with appropriate preventive dentistry before therapy begins. Patients should avoid invasive dental procedures during treatment with denosumab.
The recommended dose of denosumab is 120 mg administered as a subcutaneous injection every 4 weeks in the upper arm, upper thigh, or abdomen. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia.
No formal drug-drug interactions trials have been conducted with denosumab. In clinical trials in patients with breast cancer metastatic to the bone, there was no evidence that various anticancer treatments affected denosumab systemic exposure and pharmacodynamic effect. Serum denosumab concentrations at 1 and 3 months were not altered by concomitant chemotherapy and/or hormone therapy.