Adding denosumab (Xgeva) to adjuvant aromatase inhibitor therapy improved disease-free survival for postmenopausal patients with early-stage, hormone receptor–positive breast cancer, according to results from the phase III ABCSG-18 clinical trial presented at the 2015 San Antonio Breast Cancer Symposium, held December 8–12 in San Antonio, Texas (Abstract S2-02).
Nearly all postmenopausal women with early-stage, hormone receptor–positive breast cancer are treated with an aromatase inhibitor, either alone or in sequence with tamoxifen, for 5 to 10 years after completing their initial postdiagnosis treatment, explained Michael Gnant, MD, Professor of Surgery at the Medical University of Vienna in Austria. “This is referred to as adjuvant endocrine therapy, and it compromises bone health,” he said.
“Although the [U.S. Food and Drug Administration] has approved adjuvant denosumab as a treatment to increase bone mass in breast cancer patients receiving adjuvant aromatase inhibitor therapy who are at high risk for fracture, in most health-care environments, adjuvant denosumab is only used for those patients with established osteoporosis,” Dr. Gnant continued. “Our new data suggest that this treatment should be offered to all patients with [hormone receptor]–positive breast cancer who are receiving adjuvant aromatase inhibitor therapy, irrespective of their bone health status.”
Among the 3,425 postmenopausal patients with early-stage, hormone receptor–positive breast cancer enrolled in ABCSG-18, 1,711 were randomly assigned to 60 mg of subcutaneously administered denosumab once every 6 months, and 1,709 were randomly assigned to placebo.
The researchers found that after a median follow-up of 4 years, patients assigned to denosumab had an 18% reduced risk of disease recurring compared with those assigned to placebo. In light of previously published results, which showed that adjuvant denosumab reduced fractures caused by adjuvant aromatase inhibitor therapy by 50%, the new finding reported here amplifies the benefit of adjuvant denosumab, Dr. Gnant said.
Dr. Gnant noted that this analysis was performed as a result of a recommendation from the Independent Data Monitoring Committee (IDMC) and was based on only 370 disease-free survival events. “Therefore, it does not provide perfectly undisputable statistical power and will have to be confirmed by future analyses with longer follow-up,” he said. “I do not, however, have any doubt about the validity of the results, given the fact that the outcome benefits show clearly so early in the follow-up and are numerically bigger than we have seen in the past with bisphosphonates.
“It is also important to mention that the IDMC recommended ‘patients choice’ unblinding of this placebo-controlled trial because of the dramatic benefit in terms of fractures,” Dr. Gnant added. “This will occur in 2016, offering eligible trial patients the option of unblinding and subsequent treatment with denosumab if it turns out that they were in the placebo group.”
This study was supported by Amgen. Dr. Gnant has received grants unrelated to this study from Sanofi-Aventis, Novartis, Roche, GlaxoSmithKline, Pfizer, and Smith Medical, and has received personal fees for consulting work unrelated to this study from Novartis, Roche, GlaxoSmithKline, AstraZeneca, Nanostring Technologies, and Accelsiors.
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