Xgeva demonstrates noninferiority in delaying time to bone complications in multiple myeloma

Denosumab demonstrated noninferiority compared with zoledronic acid in delaying time to first on-study skeletal-related event in patients with multiple myeloma, according to a press release issued by the drug’s manufacturer.

However, the phase 3 study’s secondary endpoints of superiority in delaying time to first skeletal-related event and delaying time to first and subsequent skeletal-related events were not met.

“Bone complications like fracture, spinal cord compression and radiation or surgery to bone are devastating for multiple myeloma patients. Many of these patients suffer from renal impairment, which has limited their treatment options,” Sean E. Harper, MD, executive vice president of research and development at Amgen. “XGEVA's unique mechanism of action has the potential to prevent bone complications in multiple myeloma patients regardless of their renal status, fulfilling an important unmet medical need.”

Researchers compared denosumab (Xgeva, Amgen) with zoledronic acid in the international, randomized, double blind, multicenter ‘482 study. The trial included 1,718 patients with multiple myeloma who were randomly assigned to receive 120 mg subcutaneous denosumab with IV placebo every 4 weeks, or 4 mg IV zoledronic acid and subcutaneous placebo every 4 weeks.

The study’s primary endpoint — noninferiority of denosumab vs. zoledronic acid for time to first on-study skeletal-related event, which included fracture, radiation to bone, surgery to bone or spinal cord compression — was met (HR = 0.98; 95% CI, 0.85- 1.14), according to the press release.

The HR of denosumab vs. zoledronic acid for OS was 0.9 (95% CI, 0.7-1.16).

Adverse events observed in patients who received denosumab appeared comparable with the agent’s known safety profile. The most common adverse events in this study arm included diarrhea and nausea.