TY - JOUR
T1 - Denosumab for patients with persistent or relapsed hypercalcemia of malignancy despite recent bisphosphonate treatment
AU - Hu, Mimi I.
AU - Glezerman, Ilya
AU - Leboulleux, Sophie
AU - Insogna, Karl
AU - Gucalp, Rasim
AU - Misiorowski, Waldemar
AU - Yu, Bennett
AU - Ying, Wendy
AU - Jain, Rajul K.
PY - 2013/9/18
Y1 - 2013/9/18
N2 - Hypercalcemia of malignancy (HCM), caused primarily by tumor-induced bone resorption, may lead to renal failure, coma, and death. Although HCM can be treated with intravenous bisphosphonates, patients may not respond or may relapse on therapy. Denosumab binds the bone resorption mediator RANKL. In this single-arm, open-label, proof-of-concept study, HCM patients with albumin-corrected serum calcium (CSC) levels greater than 12.5 mg/dL (Common Terminology Criteria for Adverse Events grade ≥3) despite recent intravenous bisphosphonate treatment received subcutaneous denosumab on days 1, 8, 15, and 29, and then every 4 weeks. The primary endpoint was the proportion of patients with CSC 11.5 mg/dL or less (grade ≤1) within 10 days of denosumab initiation. In a prespecified interim analysis, 15 patients received denosumab (median CSC = 13.6 mg/dL). Time to response and response duration were analyzed with Kaplan-Meier methods. All statistical tests were two-sided. By day 10, 12 patients (80%; 95% exact confidence interval [CI] = 52% to 96%) responded (CSC ≤11.5 mg/dL); median response duration was 26 days. Ten patients (67%; 95% exact CI = 38% to 88%) had complete responses (CSC ≤10.8 mg/dL) by day 10. Denosumab may offer a new treatment option for HCM.
AB - Hypercalcemia of malignancy (HCM), caused primarily by tumor-induced bone resorption, may lead to renal failure, coma, and death. Although HCM can be treated with intravenous bisphosphonates, patients may not respond or may relapse on therapy. Denosumab binds the bone resorption mediator RANKL. In this single-arm, open-label, proof-of-concept study, HCM patients with albumin-corrected serum calcium (CSC) levels greater than 12.5 mg/dL (Common Terminology Criteria for Adverse Events grade ≥3) despite recent intravenous bisphosphonate treatment received subcutaneous denosumab on days 1, 8, 15, and 29, and then every 4 weeks. The primary endpoint was the proportion of patients with CSC 11.5 mg/dL or less (grade ≤1) within 10 days of denosumab initiation. In a prespecified interim analysis, 15 patients received denosumab (median CSC = 13.6 mg/dL). Time to response and response duration were analyzed with Kaplan-Meier methods. All statistical tests were two-sided. By day 10, 12 patients (80%; 95% exact confidence interval [CI] = 52% to 96%) responded (CSC ≤11.5 mg/dL); median response duration was 26 days. Ten patients (67%; 95% exact CI = 38% to 88%) had complete responses (CSC ≤10.8 mg/dL) by day 10. Denosumab may offer a new treatment option for HCM.
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U2 - 10.1093/jnci/djt225
DO - 10.1093/jnci/djt225
M3 - Article
C2 - 23990665
AN - SCOPUS:84886921988
SN - 0027-8874
VL - 105
SP - 1417
EP - 1420
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 18
ER -