Researchers involved in a multicenter Phase III study have reported that denosumab is at least as effective as Zometa® (zoledronic acid) in delaying skeletal-related events (SREs) in cancer patients with bone metastases. The details of this study were presented at the ECCO 14- ESMO 34 Congress in Berlin on September 20 as a late-breaking abstract.[1]

Denosumab is a fully human monoclonal antibody that specifically targets the receptor activator of nuclear factor kappa B ligand (RANKL), a key mediator of the resorptive phase of bone remodeling. Denosumab is being studied across a range of conditions, including osteoporosis, treatment-induced bone loss, rheumatoid arthritis, bone metastases, and multiple myeloma. A biologics license application (BLA) has recently been submitted to the U.S. Food and Drug Administration for denosumab to be used in the treatment and prevention of postmenopausal osteoporosis in women and treatment and prevention of bone loss among patients undergoing hormone ablation for breast or prostate cancer.

The current study involved 1,776 patients who had bone metastases from solid tumors or multiple myeloma. Patients with prostate and breast cancer were excluded from this trial. Patients were randomly allocated to receive denosumab or Zometa with the primary endpoint being time to first on-study SRE. Time to first SRE was 20.6 months for patients receiving denosumab and 16.3 months for patients receiving Zometa.  However, this difference was not statistically significant for superiority of denosumab over Zometa (p=0.06). The time to first and second subsequent SRE was also not significantly different between the two groups (p=0.14). The time to first on-study SRE or hypercalcemia was 19.0 months for denosumab and 14.4 months for Zometa (p=0.02). Worsening of pain occurred after 57 days in the denosumab group compared with 36 days for the Zometa group. Side effects between the two drugs appeared to be equivalent. Overall survival was similar between the two treatment groups.Osteonecrosis of the jaw occurred in 10 patients receiving denosumab and 11 patients receiving Zometa.

Comments: These data suggest that denosumab is at least as effective as Zometa for palliation of bone metastases from solid tumors or multiple myeloma and may be superior. Unfortunately, osteonecrosis of the jaw appeared in equal frequency in the two groups, which is the most distressing side effect of treatment.

Reference:

[1] Henry D, vib Niis R, Vadhan-Raj S,  et al. A double blind randomized study of denosumab versus zoledronic acid for the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) and multiple myeloma). European Journal of Cancer Supplements. 2009;7:11, abstract number 20 LBA.