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Hypercalcaemia associated with Tovorafenib discontinuation in three paediatric patients

Lookup NU author(s): Dr Claire WoodORCiD, Professor Timothy CheethamORCiD, Professor Simon BaileyORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).

Abstract

© 2026 The AuthorsBackground: 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) Kilburn et al. (2024), 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 2.91 mmol/L at 21 days (Patient 1), 3.06 mmol/L at 14 days (Patient 2), and 3.58 mmol/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.

Publication metadata

Author(s): Mohamed S, Wood CL, Halliday G, Arif T, Fritzberg A, Tuckuviene R, Majiyagbe T, Hassall TE, Nicholls W, McMahon SK, Cheetham T, Bailey S

Publication type: Article

Publication status: Published

Journal: EJC Paediatric Oncology

Year: 2026

Volume: 7

Print publication date: 01/06/2026

Online publication date: 31/01/2026

Acceptance date: 22/01/2026

Date deposited: 14/04/2026

ISSN (electronic): 2772-610X

Publisher: Elsevier B.V.

URL: https://doi.org/10.1016/j.ejcped.2026.100488

DOI: 10.1016/j.ejcped.2026.100488

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