Bone is One of the Most Common Sites for Distant Metastases Affecting up to 75 percent of Patients with Advanced Breast Cancer
Cambridge, UK, (November 9, 2010) – Amgen has announced the publication of results from a pivotal Phase 3 study of 2,046 patients which compared denosumab with Zometa® (zoledronic acid) in delaying or preventing skeletal-related events (SREs) in breast cancer patients with bone metastases. An SRE consists of any of the following: a pathologic fracture, the need for radiation or surgery to ameliorate bone pathology secondary to tumour growth, or spinal cord compression. The study, published in the Journal of Clinical Oncology , found that denosumab was superior to Zometa in delaying or preventing SREs in breast cancer patients with bone metastases.
“This study shows that in advanced breast cancer patients, denosumab is effective in delaying or preventing skeletal-related events better than Zometa, the current standard of care. In addition to its strong efficacy data, denosumab is easy to administer through a subcutaneous injection and does not require renal monitoring,” said Professor Robert Coleman, Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield. “These results are important as bone metastases from cancer are a major clinical concern and can result in debilitating pathologic fractures and other skeletal-related complications, which can cause significant suffering for our patients.”
Study Results
In the study, denosumab was superior to Zometa in delaying time to first on-study SRE (hazard ratio [HR] 0.82; 95 percent CI: 0.71-0.95; P=0.01 superiority) and time to first and subsequent (multiple) SREs (hazard ratio 0.77; 95 percent CI: 0.66-0.89; P=0.001). Reduction in bone turnover markers was greater with denosumab.
The incidence of adverse events (AEs) (96 percent denosumab, 97 percent Zometa) and serious AEs (44 percent denosumab, 46 percent Zometa) was consistent with what has previously been reported for these two agents. AEs potentially associated with renal toxicity occurred in 4.9 percent of patients treated with denosumab compared to 8.5 percent in patients treated with Zometa.
Osteonecrosis of the jaw (ONJ) was seen infrequently in both treatment groups (20 patients receiving denosumab (2.0 percent) as compared with 14 patients (1.4 percent) receiving Zometa). There was no statistically significant difference in the rate of ONJ between the two treatment arms. Hypocalcaemia occurred more frequently with denosumab. No AEs of hypocalcaemia were reported as fatal, and grade 3 or 4 AEs of hypocalcaemia were similar between groups (1.6 percent denosumab, 1.2 percent zoledronic acid). Overall survival (hazard ratio 0.95, 95 percent CI: 0.81, 1.11; p=0.50) and time to cancer progression (hazard ratio 0.99, 95 percent CI: 0.89, 1.11; p=0.90) was balanced between treatment arms.
Study Design
This study was an international, randomised, double-blind, double-dummy, active-controlled study, in which breast cancer patients were randomised to receive either subcutaneous denosumab 120 mg and intravenous placebo (N=1,026), or Zometa administered intravenously as at least a 15 minute infusion at a dose of 4 mg (or equivalent creatinine clearance-adjusted dose in patients with baseline creatinine clearance = 60 mL/min) every four weeks as per the labeled instructions. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary endpoint was time to first on-study SRE.
Bone Metastases: Prevalence and Impact
Bone metastases occur in more than 1.5 million patients with cancer worldwide and are most commonly associated with cancers of the prostate, lung, and breast, with incidence rates as high as 75 percent of patients with metastatic disease .
Patients with bone metastases who experience an SRE incur significantly higher medical costs compared with those who do not experience an SRE .
About Denosumab and Amgen's Research in Bone Biology
Denosumab is the first fully human monoclonal antibody in late stage clinical development that specifically targets RANK Ligand, the essential regulator of osteoclasts (the cells that break down bone). The denosumab development program is the largest ever initiated by Amgen. This broad and deep development program demonstrates Amgen's commitment to researching and delivering pioneering medicines to patients with unmet medical needs. Amgen is studying denosumab in numerous tumour types across the spectrum of cancer-related bone diseases. Over 11,000 patients have been enrolled in the denosumab oncology clinical trials, testing the drug for the reduction of SREs in patients with breast and prostate cancer, as well as other solid tumours and multiple myeloma, for the amelioration of treatment-induced bone loss in patients with non-metastatic breast or prostate cancers, and for its potential to delay bone metastases in prostate cancer.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realise the new science’s promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people’s lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
# # #
CONTACT: Amgen, Cambridge, UK
Emma Gilbert: 07983 179507
