Bisphosphonates, denosumab recommended to treat adults with hypercalcemia of malignancy
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A new clinical practice guideline from the Endocrine Society recommends treatment with IV bisphosphonates or denosumab in addition to adequate hydration for adults with moderate hypercalcemia of malignancy.
In a paper published in The Journal of Clinical Endocrinology & Metabolism, a multidisciplinary panel of clinical experts provided guidelines for the treatment of hypercalcemia of malignancy, a common metabolic complication of cancer. The condition affects between 2% and 30% of people with cancer, depending on the cancer type and disease stage, according to the panel.
“[The guidelines] provide a clinical care workflow by etiology and severity of hypercalcemia of malignancy,” Ghada El-Hajj Fuleihan, MD, MPH, chair of the expert panel, professor of medicine at the American University of Beirut, told Healio. “They are based on a rigorous systematic review of the evidence available today with assessment of its strength using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. They take into account not only benefits and risks of drugs to be used, but also contextual factors, such as patient values and preferences, acceptability, feasibility, equity, cost, and cost-effectiveness. In addition, patients with hypercalcemia of malignancy were surveyed to assess which hypercalcemia of malignancy outcomes they would prioritize.”
Adequate hydration and avoiding factors that worsen the condition is the recommended course for adults with mild hypercalcemia of malignancy. The first and strongest recommendation in the guideline states that treatment for adults with moderate hypercalcemia of malignancy should be an IV bisphosphonate, such as zoledronic acid, or denosumab (Xgeva, Amgen). When given the option, the guideline recommends the use denosumab over a bisphosphonate. For adults with severe hypercalcemia of malignancy, defined as having a serum calcium level of greater than 14 mg/dL, a combination of a calcitonin and an IV bisphosphonate or denosumab should be used, though calcitonin treatment should be limited to 48 to 72 hours due to the risk for tachyphylaxis.
The use of an IV bisphosphonate or denosumab is recommended for adults with tumors associated with high calcitriol levels who are already receiving glucocorticoid therapy. For adults with refractory or recurrent hypercalcemia of malignancy receiving an IV bisphosphonate, the panel recommends the use of denosumab as well.
The panel included three recommendations focused on adults with hypercalcemia due to parathyroid carcinoma. For that population, treatment with either a calcimimetic or IV bisphosphonate or denosumab is recommended, depending on the severity of the hypercalcemia at the start of treatment. Adults whose hypercalcemia is not adequately controlled despite the use of a calcimimetic should have an IV bisphosphonate or denosumab added to treatment. Similarly, those who start treatment with a bisphosphonate or denosumab and have uncontrolled hypercalcemia should have a calcimimetic added to their treatment regimen.
With the exception of the first recommendation, all of the panel’s recommendations were of low certainty of evidence due to research gaps, according to Fuleihan. One of these gaps is the lack of a placebo-controlled trial using denosumab in a group of adults with hypercalcemia of malignancy. Fuleihan said such a trial would be unethical to conduct due to the availability of IV zoledronic acid. Several other large research gaps exist, however.
“[There is a] lack of head-to-head comparison between zoledronic acid and denosumab in hypercalcemia of malignancy and lack of head-to-head comparison between cinacalcet, denosumab and intravenous zoledronic acid,” Fuleihan said.
For more information:
Ghada El-Hajj Fuleihan, MD, MPH, can be reached at gf01@aub.edu.lb.
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