Denosumab Reduces Clinical Fracture Risk in Postmenopausal Women Receiving Aromatase Inhibitors
In a phase III trial (ABCSG-18) reported in The Lancet, Gnant et al found that adjuvant denosumab (Xgeva) reduced the risk of clinical fracture in women with breast cancer receiving aromatase inhibitor therapy.
Study Details
In the double-blind study, 3,420 women from Austria and Sweden with early hormone receptor–positive breast cancer receiving aromatase inhibitors were randomized between December 2006 and July 2013 to receive subcutaneous denosumab 60 mg (n = 1,711) or placebo (n = 1,709) every 6 months.
The primary endpoint was time to first clinical fracture on intention-to-treat analysis. Patients were treated until the prespecified number of 247 first clinical fractures was reached.
Patients had a median age of 64 years. At baseline, 55% had normal total lumbar spine bone mineral density (T score ≥ –1.0), and the remainder had T scores lower than –1.0. Overall, 16% of patients started aromatase inhibitor therapy at the time of randomization, with the remainder having been on treatment for a median of 1 month prior to randomization. In total, 25% of patients had also received (neo)adjuvant chemotherapy.
Reduced Fracture Risk
Based on 268 primary endpoint events, time to first clinical fracture was significantly delayed in the denosumab group vs the placebo group (hazard ratio [HR] = 0.50, P < .0001). Estimated fracture rates at 36 months were 5.0% vs 9.6%. Denosumab was associated with a preventive benefit both among patients with a baseline bone mineral density T score of –1 or higher (n = 1,872, HR = 0.44, P < .0001) and among those with T scores less than –1 (n = 1,548, HR = 0.57, P = .002).
Adverse Events
Rates of adverse events of any grade were similar in the denosumab and placebo groups (80% vs 79%), as were rates of serious adverse events (30% in both groups). The most common adverse events were arthralgia (26% in both; total musculoskeletal and connective tissue events in 49% and 47%) and other aromatase inhibitor–related symptoms. No cases of osteonecrosis of the jaw were reported. One death considered potentially related to treatment was reported in a patient who received denosumab.
The investigators concluded, “Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures in postmenopausal women with breast cancer receiving aromatase inhibitors and can be administered without added toxicity. Since a main side effect of adjuvant breast cancer treatment can be substantially reduced by the addition of denosumab, this treatment should be considered for clinical practice.”
Michael Gnant, MD, of Medical University of Vienna, is the corresponding author of The Lancet article.
The study was funded by Amgen.
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