Amgen has presented data from a phase 3, head-to-head trial of Denosumab versus Zometa (zoledronic acid) in the treatment of bone metastases in 2,046 patients with advanced breast cancer.
In this trial, Denosumab met both primary and secondary endpoints and demonstrated superiority for delaying the time to the first on-study skeletal related events (SRE) and the time to the first-and subsequent SREs (multiple SREs).
Denosumab is the first human monoclonal antibody in late stage clinical development that targets RANK Ligand, the essential regulator of osteoclasts (the cells that break down bone).
The Phase 3 study was an international, randomised, double-blind study comparing denosumab with Zometa in the treatment of bone metastases in patients with advanced breast cancer.
Patients enrolled in the study were randomised in a one-to-one ratio to receive either 120mg of Denosumab subcutaneously every four weeks (Q4W) or Zometa administered intravenously at a dose of 4mg in a 15 minute infusion every four weeks as per the label instructions.
The primary endpoint was to evaluate if denosumab is non-inferior to Zometa with respect to the first, on-study SRE in patients with advanced breast cancer and bone metastases. Secondary endpoints were to evaluate if Denosumab was superior to Zometa with respect to the first, on-study SRE, as well as the first-and-subsequent on-study SREs, and to assess the safety and tolerability of Denosumab compared to Zometa.
Other endpoints included time to radiation of bone, time to on-study SRE or hypercalcemia of malignancy (HCM), skeletal morbidity rate (SMR, the number of SREs per year), and the proportion of patients with at least 1 on-study SRE.
Additional data from this study showed that denosumab reduced the mean annual skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) compared to Zometa.
Alison Stopeck, associate professor of Medicine at Arizona Cancer Center, said: “In clinical trials testing new medications for bone metastases, treatment success is measured by whether the bone complications, or skeletal related events, caused by the tumor are reduced or delayed.
“Skeletal complications from bone metastases are a critical and painful health concern for patients with advanced breast cancer, and can increase the risk of mortality. Patients who have a first skeletal related event are twice as likely to experience a subsequent SRE, so it is imperative to treat these advanced breast cancer patients.”