1513PRISK FACTORS FOR HYPOCALCEMIA IN PATIENTS WITH CANCER RECEIVING DENOSUMAB

ABSTRACT Aim: The potent RANK ligand inhibitor denosumab (Dmab) can cause hypocalcemia (hypoCa). Patients (pts) with inadequate intake of Ca and vitamin D are at increased risk for hypoCa. Additional baseline risk factors for hypoCa in pts with metastatic bone disease (MBD) were evaluated to aid clinical risk assessment for this adverse event. Methods: A post hoc analysis used data from three identically designed, randomized, blinded phase 3 trials comparing monthly dosing of 4 mg zoledronic acid (ZA) to 120 mg Dmab in pts with MBD to identify lab events of grade≥2 hypoCa (CTCAE: Results: The overall incidence of lab grade≥2 hypoCa events in those treated with Dmab was equal to or greater than in those treated with ZA and occurred in 12.4% of Dmab-treated pts. Baseline pt characteristics with the greatest incidence of hypoCa include: male gender (15.4%), prostate cancer (20.5%), small cell lung cancer (18.0%), and CrCl 30 – 2 bone mets and those with higher BSAP or uNTx levels (Table). Osseous lesion type did not significantly increase the risk of developing hypoCa (P ≥ 0.23). Baseline Factor Hazard Ratio 95% CI P-value > 2 bone mets 1.329 (1.044, 1.692) 0.021 BSAP>median (20.77 mg/L) 2.078 (1.579, 2.734) BSAP>median vs≤median > 2 bone mets 4.236 (2.117, 8.479) ≤ 2 bone mets 1.773 (1.312, 2.395) Interaction of baseline BSAP and # of bone mets 0.021 uNTX>50 nmol/mmol 1.316 (1.031, 1.680) 0.027 Interaction of baseline uNTX and # of bone mets 0.21 Conclusions: The risk of hypoCa after Dmab for MBD is associated with the # of bone mets and elevated bone turnover markers, especially high BSAP with>2 mets. BSAP may indicate the potential for deposition of Ca in undermineralized matrix. Pts with high bone turnover may be more susceptible to hypoCa when osteoclasts are rapidly inhibited, particularly when Ca and vitamin D intake is insufficient. Disclosure: J. Body: Consultant for and received research funding from Amgen; received honoraria from Amgen and Novartis; H.G. Bone: Consultant for and received honoraria from Amgen and Novartis; C. van Poznak: Received research funding from Amgen and Novartis; R.H. De Boer: Consultant for and received honoraria from Novartis; received research funding and other remuneration from Amgen and Novartis; A. Stopeck: Consultant for Amgen; honoraria from Amgen and GlaxoSmithKline; research funding from Amgen and Novartis; K. Fizazi: Consultant for Amgen and Novartis; honoraria from Amgen; D.H. Henry: Consultant for and received research funding and honoraria from Amgen, Ortho Biotech, and Watson; T. Ibrahim: Consultant for Amgen; A. Lipton: Honoraria and research funding from Amgen; F. Saad: Consultant for and received research funding and honoraria from Amgen and Novartis; N.D. Shore: Consultant for Amgen, Astellas, Bayer, Dendreon, Janssen, and Medivation; T. Takano: Consultant for and received honoraria from Daiichi-Sankyo; H. Wang: Employee of and owns stock or stock options in Amgen; O.L. Bracco: Employee of and owns stock or stock options in Amgen; A. Balakumaran: Employee of and owns stock or stock options in Amgen; P.J. Kostenuik: Employee of and owns stock or stock options in Amgen. All other authors have declared no conflicts of interest.