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Denosumab may be useful in treating bisphosphonate-resistant hypercalcemia of malignancy
In patients with cancer and hypercalcemia of malignancy that persists despite treatment with intravenous bisphosphonates, denosumab appears to represent a valid treatment option, according to recent findings.
In an open-label, single-arm, multicenter, international phase 2 study, researchers evaluated 33 adult patients with cancer and hypercalcemia of malignancy (HCM) resistant to IV bisphosphonate treatment. Treatment resistance was defined as corrected serum calcium (CSC) levels >12.5 ng/dL in spite of IV bisphosphonate treatment within 7 to 30 days prior.
The patients underwent a regimen of 120 mg subcutaneous denosumab on days 1, 8, 15, and 29 and every 4 weeks. Blood samples were collected for analysis of CSC and other blood chemistry on days 1, 2, 4, 8, 10, 15, 19, 23 and 29, then each week until day 57 and then monthly until the conclusion of the study. The study’s primary endpoint was proportion of patients who responded to denosumab, defined as CSC levels ≤11.5 mg/dL within 10 days of treatment.
Thirty-three percent of patients had solid tumors or hematologic malignancies.
By day 10 of the study, 64% of patients achieved the primary endpoint of CSC levels ≤11.5 mg/dL and 12 patients achieved CSC levels ≤10.8 mg/dL.
By the end of the study, 70% of patients reached CSC levels ≤11.5 mg/dL and 64% achieved CSC levels ≤10.8 mg/dL.
The median response duration was estimated to be 104 days. Hypercalcemia worsening occurred in 15% of patients and 9% experienced dyspnea.
According to the researchers, these findings represent a new option for patients who fail to adequately respond to bisphosphonate treatment.
“The response rate, the complete response rate and the prolonged duration of response observed in this study are noteworthy, because the enrolled patients had not responded or had relapsed despite bisphosphonate treatment within a media of 17 days before stud entry,” the researchers wrote. “Typically, such patients would have few therapeutic options available to them.”
Disclosure: See the full study for a complete list of the researchers’ financial disclosures.