Amgen reported results from three denosumab studies in cancer patients. A Phase II study of metastatic patients previously treated with IV bisphosphonates found that denosumab normalized a key marker of bone resorption at a greater rate than with IV bisphosphonates. Patients also experienced fewer skeletal-related events (SREs) with denosumab. A separate analysis comparing these results to another Phase II study of patients never treated with an IV bisphosphonate showed that the effect of denosumab on bone turnover markers was similar regardless of previous exposure to bisphosphonates. In addition, analysis of a Phase III trial in an earlier-stage cancer population of non-metastatic breast cancer patients showed that denosumab increased bone mineral density (BMD) at all sites measured, including cortical bone.
   
The II study evaluated patients whose urinary N-telopeptide (uNTx) levels had not normalized despite treatment with IV bisphosphonates. The primary endpoint of patients with uNTx less than 50 at week 13 was achieved by 71% of patients in the denosumab arms compared with 29% in the IV bisphosphonate arm. Denosumab also induced suppression of uNTx levels faster than IV bisphosphonate (9 days versus 65 days, respectively). At week 25, denosumab treatment was associated with fewer on-study SREs (8% versus 20%) in those receiving IV bisphosphonate therapy. Skeletal-related events include fractures, radiation or surgery to bone, and spinal cord compression.
   
The comparison of the effect of denosumab on bone turnover markers in two Phase II trials studied changes in serum-C telopeptide (sCTx), a marker of bone breakdown, from baseline to week 25. This analysis showed that at six months denosumab suppressed bone resorption by 85% in bisphosphonate-naive patients compared with 80% in patients with prior exposure to IV bisphosphonates. In patients previously treated with IV bisphosphonates, denosumab suppressed bone resorption by 80% compared with 45% in patients who continued on IV bisphosphonates.
   
Analysis of the Phase III study showed consistent increased BMD at the lumbar spine, total hip, femoral neck, and distal 1/3 radius at 12 months, regardless of duration or type of AI therapy, prior tamoxifen use, age, body mass index, or baseline T-score.