Randomized Phase II Trial of Denosumab in Patients With Bone Metastases From Prostate Cancer, Breast Cancer, or Other Neoplasms After Intravenous Bisphosphonates

• DOI: 10.1200/jco.2008.19.2146
• Publication Date: 2009-02-24T01:55:22Z
• Authors: Karim Fizazi; Allan Lipton; Xavier Mariette; Jean-Jacques Body; Yasmin Rahim; Julie R. Gralow; Guozhi Gao; Ling Wu; Winnie Sohn; Susie Jun
• Keywords: Denosumab; Urothelial cancer

Purpose Patients with bone metastases and elevated urinary N-telopeptide (uNTx), representing excessive resorption, are at increased risk for skeletal-related events (SREs), cancer progression, death. Osteoclast-mediated resorption is regulated by RANKL. We evaluated the effect of denosumab, a fully human monoclonal antibody against RANKL, in patients uNTx levels despite ongoing intravenous (IV) bisphosphonate (BP) therapy. Methods Eligible had histologically confirmed malignancy, ≥ 1 metastases, higher than 50 nmol/L collagen equivalents (BCE)/mM creatinine IV BPs. They were stratified tumor type screening (50 to 100 or > BCE/mM creatinine), randomly assigned continue BPs every 4 weeks receive subcutaneous denosumab 180 mg 12 weeks. Results Among 111 accrued, primary end point lower (uNTx < 50) week 13 was achieved 49 (71%) 69 arms, compared 10 (29%) 35 BP arm (P .001). The proportion maintained 25 (64% arms; 37% arm; P = .01). incidence SREs six (8%) 73 (17%) group group, respectively. Rates adverse similar between treatment groups. Conclusion therapy, normalized more frequently continuation BP. Fewer receiving experienced on-study those