DENOSUMAB FOR MALIGNANT HYPECALCEMIA

NEW YORK (Reuters Health) Sep 11 - Denosumab appears to reduce hypercalcemia of malignancy (HCM) that doesn't resolve with bisphosphonates, according to a planned interim analysis of an ongoing open-label proof of concept study.

"Patients who have recurrent or resistant hypercalcemia have another treatment option available for malignancy-associated hypercalcemia," Dr. Mimi I. Hu from University of Texas MD Anderson Cancer Center, Houston, Texas, told Reuters Health by email. "This can be an extremely helpful palliative measure for our patients with advanced cancer."

HCM is often treated with intravenous bisphosphonates, but up to a quarter of patients relapse and one in five may have an incomplete response.

Denosumab binds the bone resorption mediator RANKL, and in phase III studies it prevented skeletal-related events or HCM in patients with advanced malignancies involving bone.

Dr. Hu and colleagues evaluated denosumab for treatment of HCM in a proof-of-concept study of 15 patients who remained hypercalcemic despite recent IV treatment with bisphosphonates.

They reported on the prespecified interim analysis of the open-label, single-arm study, in a paper online August 29 in the Journal of the National Cancer Institute.

Patients received denosumab (120 mg subcutaneously) on days 1, 8, 15, and 29, then every four weeks until study day 57.

The median baseline corrected serum calcium level was 13.6 mg/dL (3.4 mmol/L; the range was 12.2-16.3 mg/dL, 3.1-4.1 mmol/L).

Twelve of 15 patients (80%) responded to denosumab treatments with declines in corrected serum calcium to levels of 11.5 mg/dL or less. All such responses occurred by day 10 (median, 8 days).

Eleven patients had a complete response (i.e., a corrected serum calcium level of 10.8 mg/dL or lower) during the course of the study (after a median 9 days). The median decrease in corrected serum calcium from baseline at day 10 was 2.7 mg/dL (0.68 mmol/L).

Responses were maintained for a median 26 days (range, 7 days through end of the study).

All but one patient experienced adverse events, however, and 12 (80%) had serious adverse events. Eight patients died, but none of the deaths was attributed to denosumab. Seven patients discontinued treatment for adverse events deemed unrelated to denosumab.

"I would recommend denosumab for patients with persistent or relapsed HCM due to the lack of other viable options for our patients, such as those described in our study, as our interim analysis does show a high proportion of patients will respond to denosumab despite recent use of intravenous bisphosphonates," Dr. Hu said.

She added, "We are currently in the process of analyzing the final data and developing the manuscript, which we hope to publish in the next few months."

In the meantime, she says, "Not since 2001, has there been another agent available which can effectively control hypercalcemia of malignancy. It was much needed and presents a promising advancement in medicine."

The study was sponsored by Amgen, which markets denosumab as Prolia.

SOURCE: http://bit.ly/16lmT4E

J Natl Cancer Inst 2013.