Denosumab a New Option for Preventing Skeletal-Related Events in Advanced Cancer

April 2011, Vol 2, No 2 - In the Literature


In metastatic bone disease or myeloma, bisphosphonates such as zoledronic acid (Zometa) are used to delay or prevent skeletal-related events (SREs). Although zoledronic acid is effective in delaying the onset of SREs, it is administered intravenously and can lead to treatment-associated renal complications and acute-phase reactions.

Results of a phase 3 randomized, double-blind, double-dummy study comparing the use of denosumab (Xgeva) with zoledronic acid showed that denosumab may be a more flexible option (Henry DH, et al. J Clin Oncol. 2011;29:1125-1132).

A total of 1776 patients with solid tumors and bone metastases or with osteolytic lesions from myeloma were randomized to subcutaneous denosumab and an intravenous (IV) placebo or to IV zoledronic acid and a subcutaneous placebo. The primary end point was a noninferiority comparison of the 2 treatments based on the time to a first SRE (ie, pathologic fracture, radiotherapy or surgery, or spinal cord compression).

At 34 months, denosumab was noninferior (trending toward significance) to zoledronic acid (hazard ratio, 0.84; P = .0007) in delaying the onset of a first SRE in patients with advanced cancer and bone metastasis or myeloma.

The overall survival and disease progression rates were similar between the 2 drugs, as were those of most adverse events. Hypocalcemia occurred more often with denosumab; acute-phase SREs after the first dose, and adverse renal events occurred more often with zoledronic acid.

The researchers concluded that in the treatment of bone metastasis, denosumab offers the convenience of subcutaneous administration, without monitoring for renal or acute-phase reactions. The FDA approved denosumab last year for the prevention of SREs in patients with metastatic cancer