Selumetinib as a Target Therapy in Progressive Paediatric Low-Grade Gliomas-Case Series (pLGG)

Optic pathway gliomas (OPGs) occur in 15%-20% of children with neurofibromatosis type 1 (NF1). While smaller gliomas may be only monitored, the current standard of care for symptomatic ones relies on chemotherapy, most commonly carboplatin and vincristine. These drugs can achieve tumour control but are associated with significant toxicity and do not generally restore visual function. Selumetinib, a selective MEK inhibitor, has shown efficacy in reducing NF1-related plexiform neurofibromas and has emerged as a promising targeted therapy for NF1-associated low-grade gliomas.

To retrospectively evaluate the efficacy and safety of selumetinib in children with NF1-associated progressive OPGs, with attention to radiological and functional visual outcomes.

We reviewed three paediatric patients with NF1 and progressive OPGs treated with selumetinib at 25 mg/m²/day. In one case, selumetinib was initiated as second-line after tumour regrowth following chemotherapy; in the other two, it was administered as first-line under compassionate use. Tumour response was assessed by MRI, visual function with serial ophthalmological evaluations.

All patients showed radiological tumour shrinkage or stabilization with clinically meaningful improvements in visual acuity. One child achieved near-complete recovery of vision. Treatment was well tolerated: adverse events were mild, predominantly dermatological. No severe systemic toxicities were observed.

While rigorous clinical trial data is still emerging, these preliminary cases suggest selumetinib may be a safe and effective therapeutic option for NF1-related OPGs, offering significant tumour control with a favourable toxicity profile compared to chemotherapy. Beyond stabilization, its potential to restore visual function represents a major advance, supporting the potential role of MEK inhibition as a first- and second-line treatment strategy.