Effects of denosumab in patients with bone metastases with and without previous bisphosphonate exposure

Oxford University Press (OUP) - Tập 25 Số 3 - Trang 440-446 - 2010
Jean‐Jacques Body1, Allan Lipton2, Julie R. Gralow3, Guenther G. Steger4, Guozhi Gao5, Howard Yeh6, Karim Fizazi7
1CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
2Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania
3University of Washington Cancer Care Alliance, Seattle, Washington
4Medical University of Vienna, Vienna, Austria
5Amgen Inc., San Francisco, California.
6Amgen, Inc., Thousand Oaks, California
7Department of Medicine, Institut Gustave Roussy and University of Paris XI, Villejuif, France

Tóm tắt

Abstract Bone metastases place patients at increased risk of skeletal-related events (SREs), including pathologic fractures, spinal cord compression, severe pain requiring radiotherapy or surgery, and hypercalcemia, because of increased osteoclast-mediated bone resorption. Denosumab, a fully human monoclonal antibody, decreases bone resorption by inhibiting RANKL, which mediates osteoclast activity. We compared the effects of denosumab in two phase 2 studies in patients with bone metastases naive to intravenous bisphosphonate therapy (IV BP; n = 255) and those with elevated levels of the bone resorption marker urinary N-telopeptide (uNTX) despite ongoing IV BP treatment (n = 111). Patients were randomized to receive IV BP every 4 weeks or subcutaneous denosumab every 4 weeks (30/120/180 mg) or every 12 weeks (60/180 mg). Patients treated with denosumab experienced a rapid and sustained reduction in bone turnover regardless of prior IV BP exposure. After 25 weeks, the median uNTX reduction was 75% (IV BP-naive) and 80% (prior IV BP) after denosumab treatment and 71% (IV BP-naive) and 56% (prior IV BP) in the IV BP arms. Denosumab patients with prior IV BP exposure had marked suppression of the osteoclast marker TRAP-5b (median reduction: denosumab 73%, IV BP 11%). SRE incidence was low across both studies. In patients previously treated with BPs, the rate of first on-study SRE was lower in the denosumab groups (8%) than the IV BP group (17%). Denosumab appeared to be well tolerated in both studies. Denosumab suppresses bone resorption markers independently of prior BP treatment, even in patients who appear to respond poorly to BPs. © 2010 American Society for Bone and Mineral Research.

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Oxford University Press (OUP)

Tập 25 Số 3

440-446

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