SABCS: Humanized Antibody Eases Bone Density Loss Linked to Aromatase Inhibitors

Michael Smith
SAN ANTONIO, Dec. 16 -- For the accelerated bone loss and increased risk of fracture associated with aromatase inhibitors for breast cancer, an investigational humanized antibody produced consistent increases in lumbar spine density, a researcher said here. Four of every five women in a 252-patient randomized trial treated with denosumab, delivered subcutaneously twice yearly, had at least a 3% increase in lumbar spine bone density over two years, compared with 13% for women on placebo, according to Georgiana Ellis, M.D., of the University of Washington in Seattle. Most patients in each arm of the phase III study of nonmetastatic disease had adverse events, with slightly more serious events -- 19 versus 11 -- in the denosumab arm, Dr. Ellis told a late-breaking trials session at the San Antonio Breast Cancer Symposium.
Action Points --->
Explain to interested patients that some of the important medications used to treat breast cancer, such as aromatase inhibitors, have the side effect of reducing bone density, increasing the risk of broken bones.
Note that this study reports that an investigational drug to prevent such bone loss appears to be safe and effective, but add that it is not FDA-approved for general clinical use.
Note that this agent is not FDA approved.
This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.
None of the serious adverse events was considered to be related to the study drug, Dr. Ellis said.
Loss of bone mass with aromatase inhibitor therapy is often treated with bisphosphonates, but Dr. Ellis said the humanized antibody has an "elegant mechanism of action" that is different from bisphosphonates.
The drug blocks the interaction between RANK and its ligand. The inhibition of RANK means osteoclasts cannot fuse into multi-nucleated cells, which in turn results in a reduction of bone resorption, Dr. Ellis said.
In addition to placebo or denosumab, women were given daily supplements of 1,000 mg of calcium and 400 or more international units of vitamin D.
The primary endpoint was the percentage change in bone density at the lumbar spine at 12 months, Dr. Ellis said. The researchers found that there was a significant increase in lumbar spine bone density for those getting denosumab within a month of the start of therapy and at every subsequent measurement.
At the 12-month endpoint, those getting denosumab had an average 4.7% increase in bone density from baseline and -- since those on placebo lost bone -- a 5.5% difference from placebo. The difference was significant at P<0.0001.
A year later, the difference between denosumab and placebo had increased to 7.6%, Dr. Ellis reported.
The researchers also found a 3.7% difference from placebo in total hip bone density and femoral neck bone density, Dr. Ellis said.
While the medication is not yet approved, Dr. Ellis said, "it is clearly going to be useful for patients who have difficulties with bisphosphonates."
The study is "pretty solid evidence that denosumab has a bone-sparing effect," although more research is needed, commented C. Kent Osborne, M.D., of Baylor College of Medicine in Houston, who was not involved in the study.
Dr. Osborne, co-director of the symposium, said the drug "could be a useful agent in patients taking aromatase inhibitors to prevent the bone loss that's often seen." He also praised the twice-yearly delivery.
He added that, because denosumab has a different mechanism than the bisphosphonates, "it raises the possibility of being particularly effective combined."
The study was supported by Amgen. Dr. Ellis reported financial links with the company.
Primary source: Breast Cancer Research and TreatmentSource reference:Ellis G, et al "A phase 3 study of the effect of denosumab therapy on bone mineral density in women receiving aromatase inhibitors for non metastatic breast cancer" Breast Cancer Res Treat 2007; 106 (Supp1): Abstract 47.