FDA Approves New Indication for Denosumab (Xgeva)

Megan Brooks


December 09, 2014

The US Food and Drug Administration (FDA) has approved a new indication for denosumab (Xgeva, Amgen) for the treatment of hypercalcemia of malignancy (HCM) refractory to bisphosphonate therapy, according to a company statement.

For HCM, denosumab is administered as a subcutaneous injection (120 mg) every 4 weeks, with additional doses of 120 mg on days 8 and 15 of the first month of therapy.

HCM is a serious complication of advanced cancer. It occurs most often in patients with squamous cell cancer (eg, lung cancer, head and neck cancer), breast cancer, kidney cancer, myeloma, and lymphoma. In 2012, an estimated 2.7% of US patients with cancer developed HCM. If left untreated, HCM can lead to renal failure, progressive mental impairment, coma, and death.

The approval of denosumab for HCM was based on positive results from an open-label, single-group study of patients with advanced cancer and persistent HCM after recent bisphosphonate treatment.

The primary endpoint was the proportion of patients with a response, defined as an albumin-corrected serum calcium level of 11.5 mg/dL or less (2.9 mmol/L) within 10 days after the first dose of denosumab, according to the statement.

The study achieved its primary endpoint with a response rate at day 10 of 63.6% in the 33 patients evaluated. The estimated median time to response was 9 days, and the median duration of response was 104 days.

The most common adverse reactions were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.

Denosumab is a fully human monoclonal antibody that targets the receptor activator of the nuclear factor-kappa-B ligand (RANKL) protein, which contributes to bone maintenance.

Denosumab was first approved by the FDA in June 2010 for the treatment of osteoporosis, and later that year for use in preventing skeletal-related events in adults with solid tumors and bone metastases. In 2013, the drug received FDA clearance for adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.


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