The FDA has approved a new indication for denosumab (Xgeva, Amgen) to treat hypercalcemia of malignancy refractory to bisphosphonate therapy, according to a press release from the manufacturer.
The agency based approval on results from an open-label, single-arm study that included patients with advanced cancer and persistent hypercalcemia after recent treatment with bisphosphonates. The proportion of patients with a response, defined as albumin-corrected serum calcium (CSC) <11.5 mg/dL) within 10 days after the first dose of denosumab, served as the primary endpoint.
Results showed that the study met its primary endpoint. The overall complete response rate was 63.6%, with an estimated median time to response of 9 days and a median duration of response of 104 days. Nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation and diarrhea were the most common adverse reactions, according to the release.
In patients with hypercalcemia of malignancy, denosumab is administered as a 120-mg subcutaneous injection every 4 weeks with additional doses of 120 mg on days 8 and 15 of the first month of therapy.
Denosumab works by binding to RANK Ligand (RANKL), a protein that plays a key role in the formation, function and survival of osteoclasts and, in this manner, modulates calcium release from the bone. The drug prevents decreasing bone destruction and calcium release by preventing RANKL from activating its receptor, RANK, on the surface of the osteoclasts.
Hypercalcemia of malignancy — a serious complication in patients with advanced cancer — indicates poor prognosis, and if untreated, can cause renal failure, progressive mental impairment, coma and death. Cancer-driven increases in bone resorption are responsible for the condition.
“This latest FDA approval of Xgeva provides an important new therapeutic option for patients with a rare condition that cannot be resolved with bisphosphonate therapy,” Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in the release.