Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4/6 inhibitors

Breast. 2025 Aug:82:104502. doi: 10.1016/j.breast.2025.104502. Epub 2025 May 15.

Abstract

A comparative analysis of Denosumab (DMAB) and Zoledronic Acid (ZA) was conducted in a real-world cohort of 864 patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer with bone metastases, who were undergoing CDK4/6 inhibitors plus endocrine therapy. We evaluated the time to first skeletal-related events (SREs), progression-free survival (PFS), and overall survival (OS). To adjust for confounding variables, we utilized propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methodologies. In the unadjusted cohort, ZA was associated with a longer time to first SRE compared to DMAB (HR = 0.77, 95 % CI: 0.61-0.98, p = 0.031). Similar results were obtained in both the PSM (HR = 0.69, 95 % CI: 0.52-0.92, p = 0.011) and IPTW cohorts (HR = 0.74, 95 % CI: 0.63-0.87, p < 0.001), with ZA-treated patients showing an extended time to first SRE compared to those treated with DMAB. No differences in PFS and OS were observed between the two cohorts.

Keywords: Bone metastasis; Breast cancer; CDK4/6 inhibitors; Denosumab; Zoledronic acid.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Density Conservation Agents* / therapeutic use
  • Bone Neoplasms* / drug therapy
  • Bone Neoplasms* / mortality
  • Bone Neoplasms* / secondary
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors
  • Denosumab* / therapeutic use
  • Female
  • Humans
  • Middle Aged
  • Progression-Free Survival
  • Propensity Score
  • Protein Kinase Inhibitors / therapeutic use
  • Retrospective Studies
  • Zoledronic Acid* / therapeutic use

Substances

  • Denosumab
  • Zoledronic Acid
  • Bone Density Conservation Agents
  • Cyclin-Dependent Kinase 6
  • Cyclin-Dependent Kinase 4
  • Protein Kinase Inhibitors
  • CDK6 protein, human