Work

Hypercalcaemia associated with Tovorafenib discontinuation in three paediatric patients

Year: 2026

Type: article

Abstract: Background We present three patients who developed symptomatic hypercalcaemia following discontinuation of the Type II RAF inhibitor, Tovorafenib. Methods We report three paediatric cases who had been enrolled in the phase 2 FIREFLY-1 (PNOC026; NCT04775485)l[1], which was investigating the safety and efficacy of Tovorafenib monotherapy in patients with relapsed or refractory paediatric low-grade glioma (pLGG) harbouring a KIAA-BRAF-fusion or BRAF V600E mutation. Hypercalcaemia was detected within weeks after discontinuation of Tovorafenib. Results Adjusted serum calcium concentrations at first presentation were 2.91mmol/L at 21 days (Patient 1), 3.06mmol/L at 14 days (Patient 2), and 3.58mmol/L at 26 days (Patient 3) following cessation of Tovorafenib. Calcium concentrations normalised following treatment with additional fluid and, in two of the patients, a single dose of bisphosphonate. Conclusion We suspect that the hypercalcaemia reflects a rebound increase in bone turnover following Tovorafenib discontinuation and recommend that monitoring bone biochemistry after treatment cessation be considered as part of management protocols.

Source: EJC Paediatric Oncology

DOI: 10.1016/j.ejcped.2026.100488