Back in April I reviewed the use of Aredia, Zometa, and denosumab for the prevention of skeletal-related events (SREs), in patients with cancer with bony metastases. SREs, defined as pain or fracture in a bone from cancer involvement, can result in the need for radiation, surgery, or other intervention, and consequently is damaging to the quality of life of patients with advanced cancer.

At that time, denosumab had been studied primarily in the treatment of osteoporosis, although a number of trials were ongoing in cancer patients.  The only published large randomized trial in cancer patients at that time compared denosumab to placebo in women with surgically-resected breast cancer who were receiving endocrine therapy.   Denosumab or placebo was administered every 6 months, with the outcomes of measuring an increase in bone density.  Denosumab was shown to be better than placebo at increasing bone density.   Measurement of SREs was not the goal of this trial.

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   In my last post, we covered an introduction to bone metastases and the use of the class of drugs known as bisphosphonates as a current standard treatment. A new investigational approach is also being tested, known as denosumab (AMG-162), which is a different from the bisphosphonates. A monoclonal antibody, denosumab is designed to attach to and inhibit an activating factor in the blood (termed a ligand) that stimulates the function of osteoclasts (the cells breaking down bone), thus providing a novel way of decreasing bone resorption. The ligand in this instance is called RANKL (which stands for Receptor Activator of Nuclear Factor-KappaBeta Ligand).

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The early research in this field was in the treatment of osteoporosis. Denosumab is given as a subcutaneous injection (under the skin), and different studies have used different time intervals between injections: 1 month, 3 months, or 6 months.

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