Julie R. Gralow, MD, Director, Breast Medical Oncology, Seattle Cancer Care Alliance, discusses the recent changes occurring in the anti-osteoclastic targeted therapies used to treat breast cancer bone metastases.
The bisphosphonates zoledronic acid (Zometa) and Pamidronate (Aredia) have traditionally been used to treat breast cancer bone metastases. These agents work by blocking the cells that cause bone destruction, which prevents the loss of bone mass.
Recently the agent denosumab (Xgeva), a RANK-ligand inhibitor, has become available. In comparison trials, at new diagnosis, between denosumab and bisphosphonates, denosumab proved superior at reducing skeletal-related events and improving other quality of life measures.
Gralow advocates for using denosumab in the first-line, when appropriate, or in the second-line after progression on zoledronic acid. Denosumab can be delivered subcutaneously with fewer concerns over serum creatinine levels or first infusion reactions.
With the addition of new agents there are now multiple choices for metastatic breast cancer. Trials have now begun to investigate dosing schedules to optimize delivery. The OPTIMIZE-2 trial examined bisphosphonate dosing schedules to determine if they should be given monthly, or every 3 months. Providing therapy every 3 months would reduce many of the adverse events associated with the treatment, such as osteonecrosis of the jaw.
