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J Clin Endocrinol Metab. 2014 Sep;99(9):3144-52. doi: 10.1210/jc.2014-1001. Epub 2014 Jun 10.

Denosumab for treatment of hypercalcemia of malignancy.

Author information

1
University of Texas, MD Anderson Cancer Center (M.I.H.), Houston, Texas 77030; Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (I.G.G.), New York, New York 10065; Institut Gustave Roussy (S.L.), Villejuif, France; Yale School of Medicine (K.I.), New Haven, Connecticut 06510; Montefiore Medical Center-Bronx (R.G.), New York, New York 10467; Endocrinology Department, Medical Center for Postgraduate Education (W.M.), Warsaw, Poland; Lee Moffitt Cancer Center and Research Institute (B.Y.), Tampa, Florida 33607; Peninsula Regional Medical Center (P.Z.), Salisbury, Maryland 21801; Institut Régional du Cancer de Montpellier-Val d'Aurelle (D.T.), Montpellier, France; California Cancer Associates for Research and Excellence (A.B.), Encinitas, California 92024; Centre Hospitalier Universitaire de Limoges-Hôpital Dupuytren (A.J.), Limoges, France; Policlinico Universitario Campus Bio-Medico (G.T.), Rome, Italy; and Amgen Inc (W.Y., A.B., R.K.J.), Thousand Oaks, California 91320.

Abstract

CONTEXT:

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.

OBJECTIVE:

We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM.

DESIGN, SETTING, AND PARTICIPANTS:

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.

INTERVENTION:

Patients received 120 mg sc denosumab on days 1, 8, 15, and 29 and then every 4 weeks.

MAIN OUTCOME MEASURES:

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.

RESULTS:

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%).

CONCLUSIONS:

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.

PMID:
24915117
PMCID:
PMC4154084
DOI:
10.1210/jc.2014-1001
[Indexed for MEDLINE]
Free PMC Article

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