Among women with bone metastases from breast cancer, the investigational drug denosumab was more effective than Zometa® (zoledronic acid) at reducing the risk of bone complications such as fracture. The results of several Phase III clinical trials have been published.
Metastatic cancer refers to cancer that has spread to distant sites in the body. Several types of cancer—including breast cancer—have a tendency to spread to the bone. Bone metastases can lead to serious problems such as fracture and spinal cord compression, and may require treatment with surgery or radiation therapy.
Bisphosphonate drugs such as Zometa are commonly used to reduce the risk of complications from bone metastases. Researchers continue, however, to explore new approaches to treatment.
Denosumab works by targeting a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). By decreasing osteoclast activity denosumab reduces bone loss due to cancer treatment, and postmenopausal osteoporosis resulting in increased BMD and reduced fractures.
To directly compare denosumab to Zometa among breast cancer patients with bone metastases, researchers conducted a Phase III clinical trial. The study enrolled more than 2,000 patients. Study participants were assigned to receive either denosumab or Zometa.
The objective of the study was to determine whether the occurrence of bone complications (“skeletal related events”) differed between the two study groups. The bone complications that were evaluated were fracture, radiation to the bone, surgery to the bone, and spinal cord compression.
Patients treated with denosumab remained free of bone complications longer than patients treated with Zometa.
Another trial demonstrated that denosumab increases bone mineral density (BMD) and reduces the risk of fractures in women with postmenopausal osteoporosis and individuals with cancer treatment related bone loss. Denosumab is marketed as Prolia® for the treatment of postmenopausal women with osteoporosis at high risk for fracture and as Xgeva for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.
Researchers conducted an international Phase III clinical trial known as the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) Trial. The study enrolled 7,808 women between the ages of 60 to 90, all of whom had osteoporosis.2 Half were treated with denosumab twice a year for three years and the other half received placebo. All study participants also received calcium and vitamin D.
- Women treated with denosumab were 68% less likely to develop a vertebral fracture and 40% less likely to develop a hip fracture than women in the placebo group.
These results provide additional evidence regarding the efficacy of denosumab in reducing the risk of bone fractures among women with osteoporosis.
References:
- National Institute of Arthritis and Musculoskeletal and Skin Diseases. Osteoporosis Overview. Available here (Accessed September 16, 2008).
- Cummings SR, San Martin J, McClung MR et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. New EnglandJournal of Medicine. Early online publication August 11, 2009.
- Amgen press release. Denosumab demonstrates superiority over Zometa in pivotal phase 3 head-to-head trial in breast cancer patients with bone metastases. Available here Accessed July 8, 2009.
