As reported by Gnant et al in The Lancet Oncology, disease-free survival (DFS) was improved with adjuvant denosumab vs placebo in postmenopausal women with hormone receptor–positive, early-stage breast cancer receiving aromatase inhibitor treatment. A primary analysis of the phase III ABCSG-18 trial showed a significant reduction in clinical fractures with denosumab.
In the double-blind trial, 3,425 patients from 58 sites in Austria and Sweden who had completed initial adjuvant treatment and were receiving aromatase inhibitors were randomly assigned between December 2006 and July 2013 to receive subcutaneous denosumab 60 mg (n = 1,711) or placebo (n = 1,709) every 6 months during aromatase inhibitor therapy. Disease-free survival was assessed in the intention-to-treat population.
After median follow-up of 73 months, disease-free survival events had occurred in 14.0% of patients in the denosumab group vs 16.8% of patients in the placebo group (hazard ratio = 0.82, P = .0260). Disease-free survival was 89.2% vs 87.3% at 5 years, and 80.6% vs 77.5% at 8 years.
Disease-free survival events were invasive locoregional recurrence in 1.3% vs 1.3%; ductal carcinoma in situ in 0.5% vs 0.5%; invasive contralateral breast carcinoma in 1.1% vs 1.3%; histologically verified distant metastases from breast cancer in 1.1% vs 1.1%; nonhistologically verified distant metastases or second primary cancer in 3.3% vs 4.0%; histologically verified second primary invasive non–breast carcinoma in 4.7% vs 5.9%; and death as first event in 2.3% vs 2.8%.
The total number of adverse events was 1,367, including 521 serious adverse events, in the denosumab group vs 1,339, including 515 serious adverse events, in the placebo group. The most common serious adverse events in the denosumab group were osteoarthritis (3.6% vs 3.4% in the placebo group), meniscus injury (1.3% vs 1.4%), and cataracts (0.9% vs 1.7%). The most common grade ≥ 3 adverse events in the denosumab group were osteoarthritis (2.6% vs 2.3%) and hypertension (1.2% vs 0.7%). One death considered to be treatment-related occurred in a patient treated with denosumab (due to pneumonia, septic kidney failure, and cardiac decompensation). No confirmed cases of osteonecrosis of the jaw or atypical femoral fractures were observed.
The investigators concluded, “Denosumab constitutes an effective and safe adjuvant treatment for patients with postmenopausal, hormone receptor–positive, early breast cancer receiving aromatase inhibitor therapy.”
Disclosure: The study was funded by Amgen. The study authors' full disclosures can be found at thelancet.com.
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