Hypocalcaemia in patients with metastatic bone disease treated with denosumab

Jean Jacques Body, Henry G. Bone, Richard H. De Boer, Alison Stopeck, Catherine Van Poznak, Ronaldo Damião, Karim Fizazi, David H. Henry, Toni Ibrahim, Allan Lipton, Fred Saad, Neal Shore, Toshimi Takano, Adam J. Shaywitz, Huei Wang, Oswaldo L. Bracco, Ada Braun, Paul J. Kostenuik

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Abstract Background This analysis was performed to further characterise treatment-emergent hypocalcaemia in patients with bone metastases receiving denosumab. Methods Laboratory abnormalities and adverse events of hypocalcaemia in patients with metastatic bone disease were analysed using data from three identically designed phase 3 trials of subcutaneous denosumab 120 mg (n = 2841) versus intravenous zoledronic acid 4 mg (n = 2836). Results The overall incidence of laboratory events of hypocalcaemia grade ≥2 was higher with denosumab (12.4%) than with zoledronic acid (5.3%). Hypocalcaemia events were primarily grade 2 in severity and usually occurred within the first 6 months of treatment. Patients who reported taking calcium and/or vitamin D supplements had a lower incidence of hypocalcaemia. Prostate cancer or small-cell lung cancer, reduced creatinine clearance and higher baseline bone turnover markers of urinary N-telopeptide of type I collagen (uNTx; >50 versus ≤50 nmol/mmol) and bone-specific alkaline phosphatase (BSAP; >20.77 μg/L [median] versus ≤20.77 μg/L) values were important risk factors for developing hypocalcaemia. The risk associated with increased baseline BSAP levels was greater among patients who had >2 bone metastases at baseline versus those with >2 bone metastases at baseline. Conclusion Hypocalcaemia was more frequent with denosumab versus zoledronic acid, consistent with denosumab's greater antiresorptive effect. Low serum calcium levels and potential vitamin D deficiency should be corrected before initiating treatment with a potent osteoclast inhibitor, and corrected serum calcium levels should be monitored during treatment. Adequate calcium and vitamin D intake appears to substantially reduce the risk of hypocalcaemia.

Original languageEnglish (US)
Article number9488
Pages (from-to)1812-1821
Number of pages10
JournalEuropean Journal of Cancer
Volume51
Issue number13
DOIs
StatePublished - Aug 8 2015

Keywords

  • Bone metastasis
  • Denosumab
  • Hypocalcaemia
  • Risk factors
  • Zoledronic acid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Body, J. J., Bone, H. G., De Boer, R. H., Stopeck, A., Van Poznak, C., Damião, R., Fizazi, K., Henry, D. H., Ibrahim, T., Lipton, A., Saad, F., Shore, N., Takano, T., Shaywitz, A. J., Wang, H., Bracco, O. L., Braun, A., & Kostenuik, P. J. (2015). Hypocalcaemia in patients with metastatic bone disease treated with denosumab. European Journal of Cancer, 51(13), 1812-1821. [9488]. https://doi.org/10.1016/j.ejca.2015.05.016