Denosumab Effective in Refractory Hypercalcemia of Malignancy
Denosumab shows promise in a single-arm, open label study of patients who failed to respond to
standard treatments for hypercalcemia of malignancy.
Shannon Aymes, MD
April 22, 2014- In patients with hypercalcemia of malignancy (HCM) who did not respond to or relapsed
after treatment with intravenous bisphosphonate, denosumab reduced calcium levels in most patients,
according to a small, recent study.
Mimi Hu, MD and researchers from the University of Texas and MD Anderson Cancer Center reported
their findings in the August 29, 2013 issue of the Journal of the National Cancer Institute.
Hypercalcemia of malignancy is associated with advanced malignancy and can lead to serious
complications with renal function, altered mentation, and death. Mechanisms leading to HCM are
increased resorption of bone and parathyroid hormone-related protein secretion by the malignant cells.
Denosumab is a human monoclonal antibody that binds to RANKL, a mediator in bone resorption. As
stated in the report, denosumab has been found in phase III studies “to prevent skeletal related events or
HCM in patients with advanced malignancies involving the bone.”
The researchers treated 15 patients with a diagnosis of HCM, as defined as an albumin-corrected calcium
level of 12.5 mg/dL or greater, and had previously received intravenous bisphosphonates. Investigators
administered subcutaneous denosumab on days 1, 8, 15, 29, and at 4 week intervals. The primary
objective of the study was to evaluate response to treatment defined as achieving a corrected calcium
level of 11.5 mg/dL or less in the first 10 days of treatment. The secondary objective of the study was to
evaluate response duration.
Of the 15 study patients, 12 patients achieved a corrected calcium level of less than 11.5 mg/dL at day 10
(80% with a 95% CI = 52 to 96%). The duration of response was approximately 26 days. Of the patients,
67% (n=10) showed a complete response to denosumab treatment defined by the investigators as a
corrected calcium of less than 10.8 mg/dL (95% CI = 38% to 88%).
Adverse events most commonly reported (20%) were nausea, hypercalcemia related to cancer
progression, and pyrexia. Serious adverse events (80%) and fatal adverse events (53%) were reported
“none of which were considered denosumab related.”
The study was limited in that it was conducted on a very small scale involving a complex patient
population. However, the “results suggest that denosumab may offer a new treatment option for HCM in
this challenging population.”
The study sponsor was Amgen Inc. and Amgen participated in the study design, collection, analysis and
interpretation of data along with the investigators.
J. Natl Cancer Inst. August 29, 2013 online