Adding denosumab to adjuvant aromatase inhibitor (AI) therapy can improve clinical outcomes in patients with hormone receptor (HR)-positive breast cancer, according to phase 3 results presented at the ASCO Annual Meeting 2022.1
“Adjuvant denosumab [given at] 60 mg every 6 months is safe and markedly reduces fractures, even long term,” said study presenter Michael Gnant, MD, of the Medical University of Vienna in Austria.
“[A]djuvant denosumab also improves disease-free survival, bone metastasis-free survival, and overall survival. Based on these results, adjuvant denosumab should be considered for routine clinical use in postmenopausal breast cancer patients on adjuvant aromatase inhibitor therapy.”
These results come from the double-blind, phase 3 ABCSG-18 trial (ClinicalTrials.gov Identifier: NCT00556374).
The trial included 3420 postmenopausal patients with HR-positive early breast cancer. They were randomly assigned to receive 60 mg of denosumab (n=1711) or matched placebo (n=1709) every 6 months, in addition to nonsteroidal AI therapy.
In the previously published primary analysis, researchers found the risk of fracture was significantly lower in the denosumab arm than in the placebo arm (hazard ratio [HR], 0.50; 95% CI, 0.39-0.65; P <.0001).2
Based on these results, the researchers offered patients the option of unblinding. A total of 554 patients chose to be unblinded. In the placebo arm, 252 patients crossed over to receive denosumab. These patients received denosumab for a median of 3 years.
At the final analysis, the median follow-up was 8 years. All patients had been off study treatment for a median of 5 years.
Nevertheless, the reduction in fracture risk persisted in the denosumab arm. There were 201 fractures in the denosumab arm and 255 fractures in the placebo arm (HR, 0.76; 95% CI, 0.63-0.92; P =.004).
At 11 years, the disease-free survival rate was significantly higher in the denosumab arm than in the placebo arm — 74.4% and 69.0%, respectively (HR, 0.83; 95% CI, 0.71-0.97; P =.02).
The rate of bone metastasis-free survival at 11 years was also higher with denosumab than with placebo — 85.7% and 81.3%, respectively (HR, 0.81; 95% CI, 0.65-1.00; P =.047).
There was a trend toward improved overall survival with denosumab. The 11-year overall survival rate was 88.8% in the denosumab arm and 83.6% in the placebo arm (HR, 0.80; 95% CI, 0.63-1.01; P =.06).
There were no new toxicities observed, Dr Gnant said. There were no reports of osteonecrosis of the jaw, despite proactive monitoring.
There was 1 confirmed case of atypical femur fracture in the denosumab arm that was caused by a fall from standing height or less. In addition, there were 3 treatment-emergent deaths in the denosumab arm, but these were considered unrelated to treatment.
Disclosures: This research was supported by Amgen in collaboration with the Austrian Breast and Colorectal Cancer Study Group. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
1. Gnant M, Frantal S, Pfeiler G, et al. Long-term outcomes of adjuvant denosumab in breast cancer: Fracture reduction and survival results from 3,425 patients in the randomized, double-blind, placebo-controlled ABCSG-18 trial. Presented at ASCO 2022; June 3-7, 2022. Abstract 507.
2. Gnant M, Pfeiler G, Dubsky PC, et al. Adjuvant denosumab in breast cancer (ABCSG-18): A multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(9992):433-43. doi:10.1016/S0140-6736(15)60995-3