Posted: Thursday, June 23, 2022
Adjuvant endocrine therapy with aromatase inhibitors has been found to compromise bone health in postmenopausal patients with hormone receptor–positive breast cancer. However, according to Michael Gnant, MD, FACS, of the Medical University of Vienna, and colleagues, concurrent administration of denosumab is safe and reduces the incidence of treatment-induced clinical fractures. The final long-term outcomes of the phase III ABCSG-18 trial, which were presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 507), continue to support the routine clinical use of this anti-RANK ligand.
A total of 3,425 postmenopausal patients with early hormone receptor–positive breast cancer undergoing aromatase inhibition were randomly assigned to receive either 60 mg of denosumab or a placebo subcutaneously every 6 months. Follow-up data were provided for a median of 8 years.
Disease-free survival was improved with denosumab compared with the placebo (309 vs. 368 events; hazard ratio [HR] = 0.83; P = .016), which resulted in an absolute 9-year disease-free survival difference of 3.5% (79.4% vs. 75.9%). According to the investigators, after censoring for late crossover and use of antiresorptive agents, the disease-free survival difference was confirmed (HR = 0.82; P = .010). Bone metastasis–free survival was improved by 19% with denosumab (HR = 0.81; P = .047); overall survival was improved by 20% and 26% based on the uncensored (127 vs. 158 events; HR = 0.80; P = .065) and censored (HR = 0.74; P = .013) analyses, respectively.
The previously reported reduction in clinical fractures appeared to persist in the long term, with 201 fractures in the denosumab group and 255 fractures in the placebo group (HR = 0.76; P = .004). No new toxicities were identified with this bone-protective dose of adjuvant denosumab; particularly, no osteonecrosis of the jaw was reported.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.