Anti-RANKL antibody for treatment of patients with bone metastasis from breast cancer

Breast cancer is known to be associated with a high incidence of bone metastases. Recent advances in treatment for breast cancer have improved patient prognosis, including those with bone metastasis, highlighting the importance of treating bone metastasis to reduce incidence of skeletal complications and to improve patients' QOL. Currently, bisphosphonates(BP), which are recommended by domestic and international clinical practice guidelines, are commonly used for the treatment of bone metastasis. However, the outcomes of BP therapy leave room for improvement in regard to their efficacy, safety, and convenience. Prior studies have indicated that RANK ligand(RANKL), a cytokine mainly expressed in osteoblasts and bone marrow stromal cells, plays an important role in bone resorption by osteoclasts, which are key mediators in the formation and progression of bone metastasis. Denosumab is a fully human monoclonal anti-RANKL antibody which suppresses differentiation, activation, and survival of osteoclasts by inhibiting the binding of RANKL to its receptor, RANK. In a phase III clinical trial, denosumab significantly decreased the time-to-first and time-to-first-and-subsequent skeletal related events(SRE), compared with zoledronic acid in advanced breast cancer patients with bone metastases. Further more, denosumab was more effective than zoledronic acid in preventing the progression of bone pain and maintaining patients QOL. In the future, treatment of bone metastases for breast cancer patients is expected to evolve further with the introduction of denosumab, which is conveniently administered by subcutaneous injection.