Denosumab for Skeletal Protection
Recently approved by the FDA for the prevention of skeletal events in advanced breast cancer patients with bone metastases, the monoclonal antibody denosumab (Xgeva) joins zoledronic acid (Zometa) and pamidronate (Aredia) as supportive care options in the updated guidelines. The recommendation is based on the findings of a phase III trial in which denosumab reduced the risks of experiencing a first skeletal event by 18% and multiple skeletal-related events by 23% relative to zoledronic acid (J. Clin. Oncol. 2010;10:5132-9)
Although treatment with denosumab did not improve overall survival or progression-free survival, the impact of the drug in reducing such events as fractures and bone pain could potentially minimize the need for surgery or radiation for skeletal complications and as such substantially improves patients’ quality of life, Dr. Carlson stressed.
Role of Biomarkers
While affirming the importance of determining the status of the estrogen receptor (ER), progesterone receptor (PR), and HER2 in the initial or recurrent work-up for stage IV disease, the revised guidelines do not address testing for CYP2D6 biomarkers prior to prescribing tamoxifen.
Although it has been suggested that testing for variations in the CYP2D6 gene can identify poor metabolizers of tamoxifen who will not benefit from the drug’s protective effects, "the biologic evidence is inconsistent and confusing," Dr. Carlson stated. As such, he noted, "the guidelines are silent on the issue of [CYP2D6] testing, which clinicians should interpret as a recommendation not to do it."
The updated NCCN Guidelines for Breast Cancer are available free of charge at the NCCN website.
Dr. Carlson disclosed receiving grant and research support from AstraZeneca Pharmaceuticals, Genentech, Pfizer, and Sanofi-Aventis US.