Osteoporosis drug has bone benefits in women treated with drugs to prevent breast cancer recurrence.
CHICAGO -- A monoclonal antibody originally developed to treat osteoporosis sharply cut the risk of fractures in postmenopausal women taking aromatase inhibitors to prevent breast cancer recurrence, a researcher said here.
In a large placebo-controlled, randomized trial, patients given denosumab (Prolia) every 6 months had half the risk of a clinically evident fracture than women not getting the drug, according to Michael Gnant, MD, of the Medical University of Vienna.
The toxicity of the drug did not differ markedly from placebo and in particular osteonecrosis of the jaw was "not an issue" in the trial, Gnant reported at the annual meeting of the American Society of Clinical Oncology. Additional details of the study were published simultaneously in The Lancet.
Fracture is an important side effect of post-surgical treatment with aromatase inhibitors, so the use of denosumab -- at the dose used to treat osteoporosis -- should be considered as a standard therapy, Gnant concluded.
Indeed, the results are not entirely surprising, commented Rob Coleman, MD, of the University of Sheffield in Sheffield, England.
In a formal discussion of the paper, he noted that earlier research in prostate cancer, involving men at risk of fracture owing to androgen deprivation therapy, was "similarly highly effective" in preventing broken bones.
"Denosumab is already approved by the FDA to treat osteoporosis," noted Harold Burstein, MD, PhD, of Dana-Farber Cancer Institute in Boston, so it makes sense that it might prevent fractures in cancer patients.
But "there were a lot of fractures" in the study and very few could be attributed to recurrence of the cancer, he told MedPage Today, which suggests that the bone side effects of the aromatase inhibitors might be more substantial than had been thought.
Denosumab is a fully human monoclonal antibody that binds with the RANK-ligand, which plays a central role bone resorption. It is approved to treat osteoporosis at a dose of 60 mg every 6 months given subcutaneously.
It's also approved (under the brand name Xgeva) to prevent skeletal-related events in breast cancer patients with bone metastases. In that setting it is given every 4 weeks at a dose of 120 mg.
Starting in 2006, Gnant and colleagues in the Austrian Breast and Colorectal Cancer Study Group enrolled 3,425 postmenopausal women with non-metastatic breast adenocarcinoma who were being treated with an aromatase inhibitor.
They were randomly assigned to get placebo or denosumab at doses and schedules approved for osteoporosis therapy. The primary endpoint of the study was the time to clinical fracture but the researchers also looked at other measure of bone health.
They are also following the patients to see if the drug has any effect on disease recurrence, but those data were not presented.
The bottom line, Gnant said, was that the cumulative number of first fractures in the placebo arm was 176 between 2006 and 2013, compared with 92 among those getting denosumab.
Those figures yielded a hazard ratio for fracture of 0.50, with a 95% confidence interval from 0.39 to 0.65, which was significant at P<0.0001, he reported.
Over a range of prespecified subgroups -- including whether baseline bone density was normal or low -- Gnant said the picture was the same: roughly a 50% drop in fractures with denosumab.
The researchers also found that patients getting the drug had increases in bone mineral density in the lumbar spine, total hip, and femoral neck at 12, 24, and 36 months of treatment.
In contrast, those not getting the drug saw their bone density drop and the differences were significant at P<0.001 at all time points and all bone sites, Gnant reported.
He added that the researchers were concerned about the possibility of osteonecrosis of the jaw, which has been reported in previous studies of anti-resorptive agents, but saw none.
As well, he said, there were no atypical fractures on the trial.
The safety of the drug, combined with its bone benefits, should change how people treat women on aromatase inhibitors, commented Erin Hofstatter, MD, of Yale School of Medicine in New Haven, Conn.
"They basically cut the fracture rate in half," she said. "This is practice-changing."
Before seeing the data, she said, she would have delayed treating bone issues in a patient with normal bone density. "This would really influence me to consider (denosumab) in a broader cohort," she said.
The other benefit, she said, is that the drug is given subcutaneously every 6 months -- a schedule and method of administration that is relatively easy for patients.
The study was supported by Amgen. Gnant disclosed relevant relationships with Amgen, Sandoz, AstraZeneca, GlaxoSmithKline, NanoString Technologies, Novartis, Roche Pharma AG, Accelsiors, Pfizer, Sanofi, and Smiths Medical.
Burstein disclosed no relevant relationships.
Coleman disclosed a relevant relationship with Novartis.
Hofstatter made no disclosures.
- Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College
American Society of Clinical OncologySource Reference: Gnant M, et al "Adjuvant denosumab in breast cancer: Results from 3,425 postmenopausal patients of the ABCSG-18 trial" ASCO 2015; Abstract 504.