Denosumab used as an adjuvant therapy in postmenopausal breast cancer patients on aromatase inhibitor therapy cut the risk of fractures in half.
Denosumab reduced the risk of fractures by half when used as an adjuvant therapy in postmenopausal breast cancer patients being treated with aromatase inhibitors (P < .0001). These results (abstract 504), from the Austrian ABCSG-18 study, were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 to June 2, in Chicago.
The study was also published in the Lancet.
“With a hazard ratio [HR] of 0.5-essentially cutting treatment-induced fractures in half-at no added toxicity, this is relevant,” said lead study author Michael Gnant, MD, of the Comprehensive Cancer Center and Medical University of Vienna. “I believe [this] will quickly become the new standard of care.”
The prospective double-blind, placebo controlled trial randomized 3,425 women 1:1 to either placebo or an every 6-month 60 mg subcutaneous injection of denosumab (the same dose prescribed for osteoporosis). Women on trial had stage I to stage III estrogen receptor (ER)-positive breast cancer.
Besides reducing the frequency of fractures in these patients, denosumab also improved bone mineral density of the lumbar spine, total hip, and femoral neck at 36 months compared with placebo (all adjusted P-values < .0001).
There were 92 fractures in the denosumab therapy arm compared with 176 fractures in the placebo arm. The number of fractures were similar in those patients who had normal bone health prior to starting the trial (HR = 0.44, P < .0001) and those who already had signs of osteoporosis (HR = 0.57, P = .0021).
Adverse event frequency was similar in the denosumab arm (80%) and the placebo arm (79%). Serious adverse events occurred in 30% of patients in both study arms. No cases of osteonecrosis were reported, and the major side effects were aromatase inhibitor related.
Adjuvant endocrine therapy, and aromatase inhibitors in particular, can diminish the bone health of both premenopausal and postmenopausal, making them more prone to osteoporosis, fractures, and osteopenia.
Gnant noted that prior aromatase inhibitor trials significantly underreported the frequency of fractures. The incidence of fractures in the current trial was 10% at 3 years in the placebo group, compared with as high as 30% reported in clinical practice data from Scandinavia. At 6 years, the frequency was approximately 19%, “indicating the true magnitude of the problem,” said Gnant.
The trial, sponsored by the drug’s manufacturer, Amgen, is the first to report adjuvant denosumab results. Another denosumab trial, D-CARE, uses a higher dose of the drug and is underway to assess its utility in women with high-risk breast cancer who are receiving either adjuvant or neoadjuvant endocrine therapy for stage II/III ER-positive disease. Trial results are expected in about 2 years.