Denosumab Non-inferior to Zoledronic Acid for Delaying Time to Skeletal-related Event

Denosumab (Xgeva) is non-inferior to zoledronic acid in delaying the time to first on-study skeletal-related event among patients with multiple myeloma, according to top-line results announced by Amgen.¹

Multiple myeloma is often accompanied by bone lesions, which can increase the risk of bone complications and cause significant morbidity. Denosumab is a RANK ligand inhibitor that prevents skeletal-related events among patients with bone metastases from solid malignancies. Researchers evaluated the impact of denosumab—in contrast with zoledronic acid—on time to bone complications in this patient population.

For the international, double-blind, phase 3 trial (NCT01345019), investigators enrolled 1178 patients with newly diagnosed multiple myeloma and randomly assigned them 1:1 to receive denosumab subcutaneously and placebo intravenously, or zoledronic acid intravenously and placebo subcutaneously every 4 weeks. The primary end point was non-inferiority of denosumab vs zoledronic acid in time to first on-study skeletal-related event, defined as a fracture, radiation to bone, surgery to bone, or spinal cord compression.

Preliminary results showed that there was no significant difference in time to first on-study skeletal-related event between the 2 treatment arms (hazard ratio, 0.98; 95% CI, 0.85-1.14), meeting the study’s primary end point.

The study did not, however, achieve its secondary end points of superiority in delaying time to first skeletal-related event and delaying time to first-and-subsequent skeletal-related events.

There was also no significant difference in overall survival between denosumab and zoledronic acid (hazard ratio, 0.90; 95% CI, 0.70-1.16).

The safety profile of denosumab was consistent with previous reports. The most common adverse events in the denosumab arm were diarrhea and nausea.

Amgen plans to submit detailed findings of this study for presentation at an upcoming medical conference and for publication.                        

Reference

1. Amgen announces positive top-line results from Xgeva (denosumab) phase 3 trial for delay of bone complications in multiple myeloma patients. Amgen website. http://www.amgen.com/media/news-releases/2016/10/amgen-announces-positive-topline-results-from-xgeva-denosumab-phase-3-trial-for-delay-of-bone-complications-in-multiple-myeloma-patients/. Updated October 20, 2016. Accessed October 21, 2016.