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.
Author(s): Fizazi K(1), Bosserman L, Gao G, Skacel T, Markus R.
Affiliation(s): Author information:
(1)Institut Gustave Roussy and University of Paris XI, 39 Rue Camille Desmoulins,
Villejuif, France. fizazi@igr.fr
Publication date & source: 2013, J Urol. , 189(1 Suppl):S51-7; discussion S57-8
PURPOSE: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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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