Denosumab (Xgeva) was non-inferior to zoledronic acid in delaying the time to skeletal-related events in patients with newly diagnosed multiple myeloma, according to a press release.1
To compare the efficacy of denosumab in delaying bone complications with that of zoledronic acid, the international, double-blind, phase 3 ‘482 study (ClinicalTrials.gov Identifier: NCT01345019) randomly assigned 1718 newly diagnosed patients with multiple myeloma to receive subcutaneous denosumab and intravenous placebo every 4 weeks, or intravenous zoledronic acid and subcutaneous placebo every 4 weeks.
Preliminary results showed no significant difference in the time to skeletal-related events between the 2 treatment arms (hazard ratio, 0.98; 95% CI, 0.85-1.14; P = .01). Median time to the first on-study skeletal-related event was 22.83 months with denosumab vs 23.98 months with zoledronic acid.
The study failed to demonstrate superiority with denosumab in delaying time to the first skeletal-related event and delaying time to the first-and-subsequent skeletal-related events.
Denosumab treatment appeared to reduce the risk of progression or death by 18% (hazard ratio, 0.82; 95% CI, 0.68-0.99; P = .036), but there was no significant difference in overall survival between the 2 groups. The most common adverse events in the denosumab arm were diarrhea and nausea.
Amgen plans to submit these new data to the U.S. Food and Drug Administration to support a potential update to the prescribing information of denosumab.
- Amgen presents new data from phase 3 Xgeva (denosumab) study in multiple myeloma patients at the 16th International Myeloma Workshop [news release]. Thousand Oaks, CA: Amgen; March 3, 2017. http://www.amgen.com/media/news-releases/2017/03/amgen-presents-new-data-from-phase-3-xgeva-denosumab-study-in-multiple-myeloma-patients-at-the-16th-international-myeloma-workshop/. Accessed March 6, 2017.