Risk factors for hypocalcaemia in patients with cancer receiving denosumab (#94)
Aim: Denosumab can cause hypocalcaemia and patients with inadequate intake of calcium and vitamin D are at increased risk. Additional baseline risk factors for developing hypocalcaemia in patients with metastatic bone disease (MBD) were evaluated to aid clinical risk assessment.
Methods: A post-hoc analysis used data from three identically designed phase 3 trials comparing monthly 4mg zoledronic acid (ZA) to 120mg denosumab in patients with MBD to identify lab events of grade ≥2 hypocalcaemia (CTCAE: <8.0–7.0mg/dL; <2.0–1.75mmol/L). Patient characteristics evaluated included: gender, tumour type, bone lesion type (osteolytic, osteoblastic, mixed), baseline calculated creatinine clearance (CrCl), number of bone metastases (mets), and baseline bone-specific alkaline phosphatase (BSAP) and urinary N-telopeptide (uNTx) levels.
Results: The overall incidence of lab grade ≥ 2 hypocalcaemia events in denosumab-treated patients was 12.4% and this was greater than in ZA-treated patients. Baseline patient characteristics associated with higher incidence of hypocalcaemia included: male gender (15.4%), prostate cancer (20.5%), small cell lung cancer (18.0%), and CrCl 30–60mL/min (15.5%). The risk of developing hypocalcaemia (HR [95% CI]) was increased in patients with >2 bone mets (1.329 [1.044, 1.692]; p=0.021), those with higher BSAP (2.078 [1.579, 2.734]; p<0.0001) or uNTx (1.316 [1.031, 1.680); p=0.027] levels and higher BSAP with >2 mets (4.236 [2.117, 8.479]; p=0.021 for interaction of baseline BSAP and number of bone mets). Osseous lesion type did not significantly increase the risk (p≥0.23).
Conclusions: The risk of hypocalcaemia after denosumab for MBD is associated with the number of bone mets and elevated bone turnover markers, especially in patients with high BSAP and >2 bone mets. BSAP may indicate the potential for deposition of calcium in undermineralised matrix. Patients with high bone turnover may be more susceptible to hypocalcaemia when osteoclasts are rapidly inhibited, particularly when calcium and vitamin D intake is insufficient.