1512P - Safety of denosumab (DMAB) in patients (pts) with stage 4 or stage 5D chronic kidney disease (CKD)

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Supportive Measures
Cancer in Special Situations
Presenter Geoffrey Block
Citation Annals of Oncology (2014) 25 (suppl_4): iv517-iv541. 10.1093/annonc/mdu356
Authors G. Block1, O. Egbuna2, S. Zeig3, P. Pergola4, B. Singh5, A. Braun2, Y. Yu2, W. Sohn2, D. Padhi2
  • 1Nephrology, Denver Nephrology, 80230 - Denver/US
  • 2Clinical, Amgen Inc, 91320 - Thousand Oaks/US
  • 3Clinical, Pines Clinical Research, 33028 - Pembroke Pines/US
  • 4Nephrology, Renal Associates, P.A., 78215 - San Antonio/US
  • 5Nephrology, Southwest Clincal Research Institute, LLC, 85284 - Tempe/US



DMAB is a human monoclonal antibody that binds to RANK ligand to inhibit osteoclast-mediated resorption and is approved to prevent skeletal-related events in pts with bone metastases from solid tumors. DMAB-induced inhibition of bone resorption may impact calcium (Ca) homeostasis, affecting serum Ca levels. This study evaluated the incidence of hypocalcemia and safety parameters of pts with stage 4 or 5D CKD who were administered two subcutaneous (SC) doses of DMAB.


Patients received two 120 mg doses of SC DMAB 28 days apart and were followed until day 113. All pts were required to have controlled secondary hyperparathyroidism and receive oral supplementation of ≥500 mg Ca and 400 IU vitamin D daily. The primary endpoint was the incidence of clinically significant, albumin-adjusted, serum Ca levels <7.0 mg/dL (1.75 mmol/L) or symptomatic hypocalcemia. Data were analyzed with descriptive statistics.


31/32 enrolled pts received 2 DMAB doses (15 stage 4; 16 stage 5D); 1 stage 4 CKD pt received 1 dose before withdrawing consent. 50% of pts were men, 78% white, and the median age was 76 years. The incidence of clinically significant hypocalcemia and adverse events at any point in the study are shown (Table). The majority (∼97%) of hypocalcemic events were mild to moderate in severity. The mean maximal serum DMAB concentrations were similar between the stage 4 and 5D CKD groups, 10.5 vs 8.17 µg/mL after dose 1 and 16.1 vs 14.5 µg/mL after dose 2.

Patients (%)
Stage 4N=16 Stage 5DN=16 AllN=32
Clinically significant hypocalcemiaa 1 (6.3) 2 (12.5) 3 (9.4)
All AEs 10 (62.5) 15 (93.8) 25 (78.1)
Hypocalcemia 3 (18.8) 10 (62.5) 13 (40.6)
Hypomagnesmia 0 (0.0) 0 (0.0) 0 (0.0)
Hypophosphatemia 0 (0.0) 1 (6.3) 1 (3.1)

aSerum Ca levels <7.0 mg/dL


While the use of DMAB was generally well tolerated in pts with stage 4 or 5D CKD, hypocalcemia events occurred despite oral Ca and vitamin D supplementation. This suggests an important role of bone resorption for the maintenance of serum Ca levels in this pt population, even among those with controlled secondary hyperparathyroidism. Stage 5D CKD pts were more likely to experience clinically significant or symptomatic hypocalcemia than stage 4 CKD pts. Use of DMAB in patients with stage 4 or 5D CKD requires careful monitoring for hypocalcemia.


G. Block: Advisor for Amgen National Advisory committee (paid) and Steering Committee. Research grants and travel reimbursement from Amgen Inc.; O. Egbuna: Employed by Amgen Inc and owns shares of Amgen stocks. No other disclosures.; S. Zeig: Research funding from Amgen Inc. No other disclosures.; P. Pergola: Have an advisory relationship with Amgen, Keryx, ZS Pharma. Received research support from Amgen. No other disclosures; A. Braun: I was employed by Amgen Inc and own Amgen Inc stocks; Y. Yu: I am employed by Amgen Inc and own Amgen Inc stocks; W. Sohn: I am employed by Amgen Inc and own Amgen stocks; D. Padhi: I am employed by Amgen Inc and own Amgen Inc stocks. All other authors have declared no conflicts of interest.