Xgeva reduces risk of skeletal events in cancer patients with bone metastases

Amgen Canada is introducing its second denosumab product—Xgeva (denosumab 120 mg/1.7 mL solution for injection). Xgeva is indicated for reducing the risk of developing skeletal-related events in patients with bone metastases from breast cancer, prostate cancer, non-small cell lung cancer and other solid tumours. Last year, Amgen introduced its first denosumab product—Prolia (denosumab 60 mg/mL solution for injection)–for the treatment of postmenopausal women with osteoporosis at high risk for fracture.Increased osteoclast activity, stimulated by RANK Ligand (RANKL), is a key mediator of bone disease in metastatic tumours. Denosumab inhibits the binding of RANKL to its receptors on osteoclasts. This inhibits osteoclast formation, function and survival, leading to decreased bone resorption and an interruption in cancer-induced bone destruction.The recommended dosage of XGEVA is 120 mg subcutaneously (SC) every four weeks. Patients (except those with hypercalcemia) should also receive at least 500 mg calcium and at least 400 IU vitamin D daily.The most common adverse reactions in patients receiving Xgeva are fatigue/asthenia, hypophosphatemia and nausea. The most frequent serious adverse reaction is dyspnea, while the most common adverse reactions resulting in Xgeva discontinuation are osteonecrosis and hypocalcemia.A recent major review summarized the clinical data on denosumab use in cancer patients with bone metastases. It reported that three major double-blind, multinational trials in adults with cancer-related bone metastases, including patients with advanced breast or prostate cancer, showed that denosumab (120 mg SC every 4 weeks) was noninferior to zoledronic acid (4 mg intravenously every 4 weeks), as determined by the median time to first skeletal-related event (primary endpoint).Denosumab treatment was superior to zoledronic acid in terms of the primary endpoint in two trials in patients with breast cancer or prostate cancer, based on secondary superiority analyses. In a third trial in patients with solid tumours excluding breast or prostate cancer, superiority of denosumab treatment versus zoledronic acid treatment was not demonstrated. The review also commented that the tolerability profile of denosumab was manageable.Osteonecrosis of the jaw occurred in 1.8% and 1.3% of patients in the denosumab and zoledronic acid groups, respectively, during the primary treatment phase; the incidence after approximately four additional months of denosumab treatment was 2.2%.Xgeva may have advantages over zoledronic acid in that it can be given by SC injection, while zoledronic acid is administered as a 15-minute intravenous (IV) infusion. In addition, Xgeva can be used without dosage adjustment or renal function monitoring in patients with impaired kidney function.ReferencesAmgen Canada Inc. Xgeva (denosumab 120 mg/1.7 mL solution for injection) product monograph. Mississauga, Ont.; May 10, 2011.Amgen Canada Inc. Prolia (denosumab 60 mg/mL solution for injection) product monograph. Mississauga, Ont.; November 29, 2010.Scott LJ, Muir VJ. Denosumab: in the prevention of skeletal-related events in patients with bone metastases from solid tumours. Drugs 2011;71:1059-69.

Xgeva reduces risk of skeletal events in cancer patients with bone metastases

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