The addition of denosumab to adjuvant hormonal therapy in postmenopausal breast cancer patients improves disease-free survival compared with placebo.
The addition of the bone-targeting drug denosumab to adjuvant hormonal therapy in postmenopausal breast cancer patients improves disease-free survival (DFS), reducing the risk of disease recurrence by 18% compared with placebo, according to the results of the Austrian Breast and Colorectal Cancer Study Group (ABCSG)-18 trial.
The results (abstract S2-02) were presented at the 2015 San Antonio Breast Cancer Symposium (SABCS), held December 8–12 in San Antonio, Texas.
“This is a very safe treatment and my clinical conclusion is that denosumab reduces the risk of disease recurrence or death, and this benefit is similar to what bisphosphonates can do and comes in addition to highly significantly reducing clinical fractures,” said study author and presenter Michael Gnant, MD, professor of surgery at the Medical University of Vienna in Austria, during a press conference. “I believe that we should offer this treatment to postmenopausal breast cancer patients on adjuvant aromatase inhibitors.”
Denosumab is a first-in-class antibody approved by the US Food and Drug Administration (FDA) in 2010 for the prevention of skeletal-related events (SREs) in patients with solid tumors and bone metastases. The antibody binds to the RANK ligand on osteoclasts in bone tissue, preventing bone destruction. Previously, bisphosphonates such as zoledronic acid were the major option for prevention of SREs.
In June, analysis of the primary endpoint of the ABCSG-18 study demonstrated that adjuvant denosumab given twice a year can cut treatment-induced fractures in half in this group of breast cancer patients. The trial randomized 3,425 patients with early-stage hormone receptor–positive disease to 60-mg subcutaneous injections of denosumab every 6 months, or to placebo.
After a median follow-up of 4 years, the current analysis of secondary endpoints showed a statistically significant improvement in DFS (hazard ratio [HR], 0.816; P = .051) among patients taking denosumab compared with those in the placebo group.
“The analysis indicates that adjuvant denosumab actually improves DFS in the intent-to-treat population,” said Dr. Gnant. “This is a borderline statistical significance but sensitivity analysis shows that this may be a conservative estimate.”
An additional exploratory subgroup analysis suggests that denosumab may particularly benefit those women with tumors larger than 2 cm (HR, 0.66; P = .016), those with ductal breast cancer histology (HR, 0.79; P = .048), and those with tumors positive for both the estrogen and progesterone receptors (HR, 0.75; P = .013).
The addition of denosumab treatment was safe, with no measurable differences in adverse events between the denosumab- and placebo-treated patients, and no confirmed cases of osteonecrosis of the jaw.
“If I see a new patient next week, I would start her on these injections [with denosumab] for 3 years,” said Gnant.