Denosumab Attenuates Bone Loss Associated with Aromatase Inhibitors

December 17, 2007

Investigational agent denosumab is safe and efficacious for attenuating bone loss among women taking adjuvant aromatase inhibitors for breast cancer, according to a phase III randomized double-blind placebo-controlled trial reported at SABCS (abstract 47).

Investigational agent denosumab is safe and efficacious for attenuating bone loss among women taking adjuvant aromatase inhibitors for breast cancer, according to a phase III randomized double-blind placebo-controlled trial reported at SABCS (abstract 47).

Georgiana K. Ellis, MD
Photo Courtesy SABCS/Todd Buchanan 2007

"Adjuvant use of aromatase inhibitors has been increasingly favored over tamoxifen," said lead author Georgiana K. Ellis, MD, of the Seattle Cancer Care Alliance. She noted, however, that "aromatase inhibitors are associated with accelerated bone loss and increased risk of fracture." The pivotal HALT Breast Cancer trial enrolled 252 women with hormone receptor-positive nonmetastatic breast cancer who were taking an aromatase inhibitor (AI) and who had osteopenia at the lumbar spine, total hip, and/or femoral neck. Women were ineligible if they had osteoporosis, were receiving additional anticancer therapies or oral bisphosphonates, or were vitamin D-deficient. After stratification by duration of AI use (≤6 vs >6 months), the women were assigned to receive denosumab -- a monoclonal antibody to the receptor activator of nuclear factor-κ B (RANK) ligand -- or placebo every 6 months. Women in both groups took calcium and vitamin D daily. Overall, 83% of women in the denosumab group and 79% in the placebo group completed the 24-month study. The percentage change from baseline in lumbar spine bone mineral density was significantly greater in the denosumab group than in the placebo group at both 12 months (5.5% difference) and 24 months (7.6% difference). Moreover, this benefit was not influenced by the duration of prior AI therapy and was also present in the total hip and the distal third of the radius, Dr. Ellis said. The rate of potentially treatment-related adverse events was similar between the denosumab and placebo groups (25% vs 26%). The rate of serious adverse events was somewhat higher in the denosumab group (15% vs 9%), but none of these were believed to be treatment related, Dr. Ellis said. The most common adverse events seemed to be mainly due to the AI therapy. The leading ones were arthralgia, extremity pain, and back pain. "Women with nonmetastatic breast cancer receiving adjuvant AI therapy benefited from administration of denosumab ... , undergoing consistent increases in bone mineral density at both trabecular and cortical bone sites over the duration of the 24-month study period. Denosumab was generally well tolerated, with overall rates of adverse events similar to what was seen for placebo," Dr. Ellis said. "These results support the ongoing clinical trial program of denosumab for the prevention and treatment of bone loss."

Disclosures:

The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.