According to the results of a Phase III clinical trial, the experimental drug denosumab significantly improves bone density among women with non-metastatic breast cancer treated with an aromatase inhibitor. These results were published in the Journal of Clinical Oncology. ?
Each year more than 180,000 U.S. women are diagnosed with breast cancer. Many of these breast cancers will be hormone receptor-positive, meaning that they are stimulated to grow by the circulating female hormones estrogen and/or progesterone.
Treatment of hormone receptor-positive breast cancer often involves hormonal therapies that suppress or block the action of estrogen. These therapies include tamoxifen (Nolvadex?) as well as agents known as aromatase inhibitors. Tamoxifen acts by blocking estrogen receptors, whereas aromatase inhibitors suppress the production of estrogen in postmenopausal women.
Although several studies have shown that aromatase inhibitors reduce the risk of breast cancer recurrence among postmenopausal breast cancer patients, they have been linked with bone loss. Use of drugs that reduce bone loss may therefore benefit women who are treated with an aromatase inhibitor.
Denosumab is an investigational drug that targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Denosumab is being evaluated for the management of bone loss among patients with a variety of conditions, including cancer patients with treatment-related bone loss and postmenopausal women with osteoporosis.
To evaluate the effects of denosumab on bone density among women treated with an aromatase inhibitor, researchers conducted a Phase III clinical trial. The trial enrolled 252 women with non-metastatic, hormone receptor-positive breast cancer. At the start of the study, all study participants had evidence of bone loss but none had osteoporosis.
All of the study participants received adjuvant treatment with an aromatase inhibitor. In addition, half the women received four doses of denosumab and half received a placebo. All patients were also asked to take calcium and vitamin D supplements.
- Compared with women in the placebo group, lumbar spine bone density among women in the denosumab group was 5.5% higher at 12 months of follow-up and 7.6% higher at 24 months of follow-up. ?
- Women treated with denosumab also had higher total body bone density and higher bone density at the hip, femoral neck, and radius.
- The overall frequency of adverse events was similar in the denosumab group and the placebo group.
These results suggest that denosumab effectively improves bone density among breast cancer patients receiving adjuvant aromatase inhibitor therapy.
Reference: Ellis GK, Bone HG, Chlebowski R et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. Journal of Clinical Oncology. 2008;26:4875-4882.