eBCa: denosumab fails to improve survival of high-risk patients in D-CARE

  • Coleman R & al.
  • Lancet Oncol
  • 2 Dec 2019

  • curated by Miriam Davis, PhD
  • Univadis Clinical Summaries
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Takeaway

  • 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.

Study design

  • 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.

Key results

  • 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

Limitations

  • Lower than expected number of events for efficacy analysis.