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Denosumab Treatment of Prostate Cancer With Bone Metastases and Increased Urine N-Telopeptide Levels After Therapy With Intravenous Bisphosphonates: Results of a Randomized Phase II Trial

Institut Gustave Roussy and University of Paris XI, Villejuif, France.
The Journal of urology (Impact Factor: 3.75). 07/2009; 182(2):509-15; discussion 515-6. DOI: 10.1016/j.juro.2009.04.023
Source: PubMed

ABSTRACT Patients with bone metastases have high rates of RANKL driven bone resorption and an increased risk of skeletal morbidity. Osteoclast mediated bone resorption can be assessed by measuring urine N-telopeptide and can be inhibited by denosumab, a fully human antibody against RANKL.
Eligible patients (111) had bone metastases from prostate cancer, other solid tumors or multiple myeloma, 1 or more bone lesions and urine N-telopeptide greater than 50 nM bone collagen equivalents per mM creatinine (urine N-telopeptide greater than 50) despite the use of intravenous bisphosphonates. Patients were stratified by cancer type and screening urine N-telopeptide, and randomized to continue intravenous bisphosphonates every 4 weeks or receive 180 mg subcutaneous denosumab every 4 weeks or 180 mg every 12 weeks. The primary end point was the proportion of patients with urine N-telopeptide less than 50 at week 13. We report the efficacy results for the subset of patients with prostate cancer.
Patients with prostate cancer represented 45% (50 of 111) of the study population. At week 13, 22 of 32 (69%) patients in the denosumab arms had urine N-telopeptide less than 50 vs 3 of 16 (19%) in the intravenous bisphosphonates cohort. At week 25, 22 of 32 (69%) denosumab treated patients continued to have urine N-telopeptide less than 50 vs 5 of 16 (31%) treated with intravenous bisphosphonates. Grade 4, asymptomatic, reversible hypophosphatemia, possibly related to denosumab, was reported in 1 patient.
In patients with prostate cancer related bone metastases and increased urine N-telopeptide despite intravenous bisphosphonate treatment, denosumab normalized urine N-telopeptide levels more frequently than ongoing intravenous bisphosphonates.

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    • "Both have shown similar promise in clinical trials, however only Denosumab is advanced through Phase III. Administration of Denosumab showed significant efficacy by inhibiting osteolysis in patients with prostate or breast cancer bone metastasis, based on the analysis of urinary Ntelopeptide levels as a marker for bone turnover (Fizazi et al., 2009, 2013). A single dosing system of recombinant OPG (AMGN-0007) in a Phase I trial demonstrated a similar sustained reduction in bone lysis (Body et al., 2003). "
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    • "Grade 4, asymptomatic, reversible hypophosphatemia, possibly related to Denosumab, was reported in one patient. The authors concluded that in patients with prostate cancer related bone metastases and increased urine N-telopeptide despite intravenous bisphosphonate treatment, Denosumab normalized urine N-telopeptide levels more frequently than ongoing intravenous bisphosphonates.[2829] "
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