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- Title
Denosumab for treatment of hypercalcemia of malignancy.
- Authors
Hu, Mimi I; Glezerman, Ilya G; Leboulleux, Sophie; Insogna, Karl; Gucalp, Rasim; Misiorowski, Waldemar; Yu, Bennett; Zorsky, Paul; Tosi, Diego; Bessudo, Alberto; Jaccard, Arnaud; Tonini, Giuseppe; Ying, Wendy; Braun, Ada; Jain, Rajul K
- Abstract
<bold>Context: </bold>Hypercalcemia of malignancy (HCM) in patients with advanced cancer is often caused by excessive osteoclast-mediated bone resorption. Patients may not respond to or may relapse after iv bisphosphonate therapy.<bold>Objective: </bold>We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM.<bold>Design, Setting, and Participants: </bold>In this single-arm international study, participants had serum calcium levels corrected for albumin (CSC) >12.5 mg/dL (3.1 mmol/L) despite bisphosphonates given >7 and ≤30 days before screening.<bold>Intervention: </bold>Patients received 120 mg sc denosumab on days 1, 8, 15, and 29 and then every 4 weeks.<bold>Main Outcome Measures: </bold>The primary endpoint was the proportion of patients with CSC ≤11.5 mg/dL (2.9 mmol/L) (response) by day 10. Secondary endpoints included response by visit, duration of response, and the proportion of patients with a complete response (CSC ≤10.8 mg/dL [2.7 mmol/L]) by day 10 and during the study.<bold>Results: </bold>Patients (N = 33) had solid tumors or hematologic malignancies. By day 10, 21 patients (64%) reached CSC ≤11.5 mg/dL, and 12 patients (33%) reached CSC ≤10.8 mg/dL. During the study, 23 patients (70%) reached CSC ≤11.5 mg/dL, and 21 patients (64%) reached CSC ≤10.8 mg/dL. Estimated median response duration was 104 days. The most common serious adverse events were hypercalcemia worsening (5 patients, 15%) and dyspnea (3 patients, 9%).<bold>Conclusions: </bold>In patients with HCM despite recent iv bisphosphonate treatment, denosumab lowered serum calcium in 64% of patients within 10 days, inducing durable responses. Denosumab may offer a new treatment option for HCM.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2014, Vol 99, Issue 9, p3144
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2014-1001