- Subcutaneous denosumab fails to extend bone metastasis-free survival (BMFS) or DFS in a large, randomized, placebo-controlled trial of high-risk early breast cancer (eBCa) patients also receiving standard-of-care systemic therapy.
Why this matters
- Bone is the most common site of relapse and the first affected site in 40% of relapsing patients.
- This is the first phase 3 trial of its kind.
- International, double-blind, randomized, placebo-controlled, phase 3 trial (D-CARE; n=4509) of denosumab (120 mg) or placebo given subcutaneously every 3-4 weeks, beginning with neoadjuvant or adjuvant chemotherapy, for about 6 months and then every 12 weeks thereafter for 5 years total duration.
- Patients were stage II or III BCa and ECOG performance status of 0 or 1.
- The primary outcome was BMFS.
- Funding: Amgen.
- Median follow-up was 67.2 months.
- No difference in DMFS (HR, 0.97; 95% CI, 0.82-1.14; median not reached in either group).
- No difference in DFS (HR, 1.04; 95% CI, 0.91-1.19).
- The most frequent grade ≥3 treatment-emergent adverse events:
- neutropenia (15% vs 15% among placebo recipients);
- febrile neutropenia (5% vs 6%); and
- leucopenia (3% vs 3%).
- Osteonecrosis of the jaw occurred in 5% vs
- Atypical femur fracture occurred in
- Lower than expected number of events for efficacy analysis.