Outcomes of Target Therapies for Paediatric BRAF V600-Mutant Low-Grade Gliomas: A systematic review and Meta-Analysis of Clinical and Observational Studies

Background This systematic review and meta-analysis evaluated the efficacy, safety, and available functional outcomes of targeted therapies, including BRAF and MEK inhibitors, in paediatric patients with BRAF V600-mutant low-grade gliomas (pLGG). The review also explored their impact on clinical management, recovery, and quality of life. Methods The review followed PRISMA 2020 guidelines. Systematic searches were conducted across PubMed, ScienceDirect, EBSCO-hosted databases, and CENTRAL. Eligible studies included RCTs and retrospective studies (RS) reporting on tumour overall response rates (ORR), progression-free survival (PFS), adverse events (AEs), and functional outcomes in patients aged 1–17 years. Risk of bias was assessed using CASP; certainty of evidence with GRADE. Meta-analyses used a random-effects model (STATA 18.5). Funnel plots, Egger’s tests and subgroup/ sensitivity analyses explored bias and heterogeneity. Results Ten studies (16 treatment arms; 4 RCTS, 6 RS were included). Pooled ORR was 42.35% (95% CI: 29.41–55.29), and the median PFS was 23.03 months (95% CI: 17.18–28.88). Grade 3/4 AEs occurred in 30.56% (95% CI: 22.60–38.53), most commonly rash, fatigue, and fever. Subgroup analyses suggested higher efficacy and lower toxicity with BRAF inhibitors or combination therapy. Functional outcomes were inconsistently reported, though some evidence suggested improvements in vision and performance status. Conclusions Targeted therapies are effective and well tolerated in paediatric BRAF V600-mutant LGG, offering a promising alternative to chemotherapy, particularly in relapsed or progressive disease. Emerging evidence suggests potential benefit in selected molecularly defined patients, however further prospective studies are required to define their role in first-linetreatment. Standardised outcome reporting and long-term follow-up are essential to optimise care.