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FDA approves Xgeva for prevention of skeletal-related events in multiple myeloma
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The FDA expanded the indication of denosumab to include the prevention of skeletal-related events among patients with multiple myeloma.
Denosumab (Xgeva, Amgen) — a human monoclonal antibody that binds and neutralizes RANK ligrand — is approved for the prevention of skeletal-related events among patients with bone metastases from solid tumors.
“Up to 40% of patients remain untreated for the prevention of bone complications, and the percentage is highest among patients with renal impairment at the time of diagnosis,” Noopur Raje, MD, director of Center for Multiple Myeloma at Massachusetts General Hospital Cancer Center, said in a manufacturer-issued press release. “Denosumab, which is not cleared through the kidneys, offers multiple myeloma patients bone protection with a convenient subcutaneous administration, providing patients with a novel treatment option.”
The FDA based the approval on results from the phase 3 randomized, double-blind ‘482 study, which included 1,718 adults with newly diagnosed multiple myeloma and bone disease.
Researchers assigned patients 1:1 to subcutaneous denosumab (120 mg) and IV placebo every 4 weeks, or IV zoledronic acid (4 mg; adjusted for renal function) and subcutaneous placebo every 4 weeks.
Results showed denosumab delayed time to first on-study skeletal related event — including pathologic fracture, radiation to bone, surgery to bone or spinal cord compression — compared with zoledronic acid (HR = 0.98; 95% CI, 0.85-1.14).
Investigators did not observe superiority for denosumab in the secondary endpoints of delaying time to first skeletal-related event and delaying time to first and subsequent skeletal-related events.
OS appeared comparable between treatment groups (HR = 0.9; 95% CI, 0.7-1.16).
Median difference in PFS among patients assigned denosumab compared with placebo was 10.7 months (46.1 months vs. 35.4 months HR = 0.82; 95% CI, 0.68-0.99).
Observed adverse events appeared consistent with the known safety profile of denosumab. The most common adverse reactions included diarrhea (34%), nausea (32%) anemia (22%), back pain (21%), thrombocytopenia (19%), peripheral edema (17%), hypocalcemia (16%), upper respiratory tract infection (15%), rash (14%) and headache (11%).
The most common adverse event leading to discontinuation of denosumab was osteonecrosis of the jaw, which was confirmed among 4.1% of patients assigned denosumab vs. 2.8% of patients assigned zoledronic acid.
“Bone complications can be devastating for patients with multiple myeloma. Previously, treatment options for the prevention of bone complications were limited to bisphosphonates which, unlike Xgeva, are cleared by the kidneys,” David M. Reese, MD, senior vice president of Translational Sciences and Oncology at Amgen, said in the release. “We are pleased that the FDA has approved the expanded indication for Xgeva, providing a new option for patients and physicians, underscoring our commitment to advancing care for patients with multiple myeloma.”
Denosumab also is indicated for the treatment of adults or skeletally mature adolescents with unresectable giant cell tumor of bone, and for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.