The US Food and Drug Administration (FDA) approved a supplemental Biologics License Application to expand the indication of denosumab to include patients with multiple myeloma, according to a press release.1
Denosumab was previously indicated for skeletal-related event prevention among patients with bone metastases from solid tumors.
The FDA based its approval on results from the double-blind phase 3 ‘482 study (ClinicalTrials.gov Identifier: NCT01345019), for which researchers randomly assigned 1718 newly diagnosed patients to receive subcutaneous denosumab 120 mg or intravenous zoledronic acid 4 mg every 4 weeks.
Denosumab was non-inferior to zoledronic acid in delaying the time to first on-study skeletal related event (hazard ratio [HR], 0.98; 95% CI, 0.85-1.14; P = .01), achieving the study’s primary endpoint.
Secondary endpoints, including superiority of denosumab to zoledronic acid in delaying time to first skeletal-related event and delaying time to first- and subsequent skeletal-related events, were not met.
The overall survival was similar for patients in both study arms (HR, 0.90; 95% CI, 0.70-1.16; P = .41). The median progression-free survival (PFS) for patients in the denosumab arm was 46.1 months (95% CI, 34.4-not evaluable) compared with 35.4 months (95% CI, 30.2-not evaluable) for patients treated with zoledronic acid (HR, 0.82; 95% CI, 0.68-0.99; descriptive-P = .036).
Denosumab is not cleared though the kidneys, providing patients with renal impairment — who are at high risk of developing bone complications — a novel therapeutic modality. Compared with zoledronic acid, patients treated with denosumab had lower rates of renal adverse events (17.1% vs 10.0%, respectively; P < .001).
The most frequently reported adverse events included diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, and upper respiratory tract infection.
- FDA approves XGEVA (denosumab) for the prevention of skeletal-related events in patients with multiple myeloma [news release]. Thousand Oaks, CA: Amgen; January 5, 2017. https://www.prnewswire.com/news-releases/fda-approves-xgeva-denosumab-for-the-prevention-of-skeletal-related-events-in-patients-with-multiple-myeloma-300578047.html. Accessed January 5, 2017.