Lay Summary Paediatric Low-Grade Glioma (PLGG) is the commonest brain tumour of childhood. Most children and young adults under eighteen years old with PLGG will survive long-term, but many will face functional or quality of life consequences from the tumour and its required treatment. Accordingly, research efforts have focused on developing new treatments which are more effective and less toxic which target the underlying genetic changes within the MAPK pathway known to cause PLGG growth. Over the last few years, these new and targeted therapies are increasingly being used in PLGG but outside of more standardised and monitored clinical trials, without consistency regarding when to start the new therapies or the required supportive care that patients receive alongside these new drugs. We provide the first national real-world efficacy and toxicity data from a large PLGG cohort receiving MAPKi outside of clinical trials in the UK. We collected data from 50 patients treated with MAPK inhibitor therapy (MAPKi) between 2016 and 2024 across 7 UK Paediatric Brain Tumour centres. We collected standardised assessments of tumour response to treatment on MRI scan (Radiological response), visual responses in those with tumours involving the optic pathway, and survival outcomes (overall survival and progression of tumours; progression-free survival). We also collected and analysed data on treatment side effects, need for dose reductions or stopping of therapy earlier than 2 years. We calculated the ratio of duration of response on MAPKi compared to prior chemotherapy which is a recognised measure of MAPKi treatment benefit. At a median period of 3.5 years from starting MAPKi therapy, 96% of patients remained alive but 38% had tumour progression. Seventy-four percent of patients had a radiological benefit from MAPKi therapy observed on MRI imaging (stable disease 54%, partial response 20%). Of 35 patients with optic pathway tumours, 72% had visual benefit from MAPKi therapy (63% stable, 9% improved). Seventy-seven patients had a prolonged MAPKi: prior chemotherapy ratio of 1.3: 1 demonstrating superior benefit from MAPKi therapy compared to prior chemotherapy. We conclude that MAPKi therapies provide safe and effective treatment for PLGG, with significantly prolonged periods without tumour progression compared to prior chemotherapy.
Green et al. (Wed,) studied this question.