Amgen Presents Phase 3 Trial Results For Denosumab

Amgen has announced detailed results from a phase 3 trial evaluating denosumab administered subcutaneously versus Zometa (zoledronic acid) administered as an intravenous infusion in the treatment of bone metastases in 1776 advanced cancer patients with solid tumors (not including breast and prostate cancer) or multiple myeloma. These results were presented at the 2009 ECCO 15 – ESMO 34 European Multidisciplinary Congress in Berlin, Germany.

For the primary endpoint of the study, the median time to first on-study skeletal related event (SRE) was 20.6 months for those patients receiving denosumab and 16.3 months for those patients receiving Zometa, which is statistically significant for non-inferiority (p=0.0007). Although numerically greater, the delay in the time to first SRE associated with denosumab was not statistically superior compared to Zometa based upon the statistical testing strategy (adjusted p=0.06) (secondary endpoint). The time to first-and-subsequent SRE was also numerically greater but not statistically superior compared to Zometa (secondary endpoint).

Denosumab also delayed the median time to first on-study SRE or hypercalcemia of malignancy (HCM) compared to Zometa. The median time to first on-study SRE or HCM was 19.0 months for denosumab and 14.4 months for Zometa.

Adverse events rates (96% denosumab, 96% Zometa) and serious adverse events (63% denosumab, 66% Zometa) were similar between groups and were consistent with what has previously been reported for these two agents. Rates of osteonecrosis of the jaw (ONJ) were balanced and infrequent in both treatment groups (10 patients receiving denosumab as compared with 11 patients receiving Zometa). Infectious adverse events were balanced between the two treatment arms, as was overall survival and the time to cancer progression.