Denosumab Tops Zometa for Bone Protection in Breast Cancer Patients

San Antonio, TX—In a head-to-head comparison of two bone-protective agents, the RANK ligand inhibitor denosumab was superior to the standard-of-care bisphosphonate, zoledronic acid (Zometa), in a study of breast cancer patients with bone metastases. The study was reported at the 32nd annual San Antonio Breast Cancer Symposium.

The randomized comparison of 2048 breast cancer patients with bone metastases evaluated the two agents for the prevention of skeletal-related events (SRE), defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression. “Denosumab prevented more events, was better tolerated, and was more convenient for patients in this randomized double-blind trial against what has been the standard of care for treating bone metastasis,” said Alison Stopeck, MD, of the University of Arizona Cancer Center, Tucson, who described the study at a press briefing.

Patients with bone metastases not previously treated with intravenous (IV) bisphosphonates were randomized to treatment with subcutaneous (SC) denosumab (120 mg every 4 weeks) and IV placebo, or SC placebo and IV zoledronic acid (4 mg every 4 weeks), in addition to supplemental calcium and vitamin D.

The primary endpoint of time to first on-study SRE was reduced by 18% with denosumab treatment. Patients receiving ZA experienced their first SRE in 26.5 months, but the median time to first SRE has not been reached in the denosumab group.

The study also evaluated the benefit of continued treatment with denosumab, since patients with SREs are at increased risk for a second event.Denosumab was also superior in that comparison, with time to first-and-subsequent on-study SREs reduced by 23%, Dr Stopeck said. Importantly for patients, she added, denosumab was associated with a delay in the onset of moderate or severe pain, which was extended from 64 days with ZA to 88 days with denosumab, a statistically significant difference.

Adverse events were reported by over 95% of patients in each arm.Patients receiving ZA had a higher incidence of acute phase reactions (27.3% vs 10.4%, respectively) and more renal toxicity (8.5% vs 4.9%, respectively). Osteonecrosis of the jaw, a concern with bisphosphonate use, was uncommon in each arm, occurring in 14 patients (1.4%) taking ZA and 20 (2.0%) taking denosumab, a difference that was not significant. The majority of patients who developed osteonecrosis had risk factors for the condition, such as dental extraction and dental appliances, Dr Stopeck said.

Press briefing moderator Theresa Guise, MD, Professor of Medicine at Indiana University School of Medicine, called the findings “very important.” She said they demonstrate that the inhibition of bone resorption through RANK ligand, which regulates osteoclast activity and function, may offer improved protection against SREs in patients with bone metastases. SABCS Abstract 22.