{"entity":{"id":"paper-hargrave-dabrafenib-trametinib-paediatric-hgg-jco-2023","kind":"paper","name":"Dabrafenib plus trametinib in relapsed or refractory BRAF V600-mutant paediatric high-grade glioma","aka":[],"tldr":"In children whose BRAF V600-mutant high-grade glioma had relapsed, the combination of dabrafenib and trametinib shrank tumours in more than half and gave responses lasting well over a year, far better than historical chemotherapy.","summary":"Phase 2 study of 41 children and adolescents with relapsed or refractory BRAF V600-mutant high-grade glioma treated with dabrafenib plus trametinib.\n\nObjective response by independent review was 56 percent with a median duration of response of 22.2 months and median progression-free survival of 9.0 months, compared with expected responses of under 20 percent with chemotherapy; toxicity was mostly fever, rash and gastrointestinal.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2023","url":"https://doi.org/10.1200/JCO.23.00558"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37643378/"}],"tags":[],"related":[],"cancers":["paediatric-high-grade-glioma"],"sections":[],"technologies":[],"targets":[],"drugs":["dabrafenib","trametinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.23.00558","pmid":"37643378","authors":"Hargrave DR, Terashima K, Hara J, et al.","paperType":"observational","findings":["Objective response 56 percent; median duration of response 22.2 months.","Median overall survival 32.8 months."],"whatItMeans":"BRAF V600E testing is mandatory in childhood high-grade glioma and the combination is a standard at relapse and, increasingly, alongside or before radiotherapy in newly diagnosed disease; it supported the tumour-agnostic approval in children.","caveats":["Small single-arm cohort.","Resistance eventually develops in most patients."],"changedPractice":true,"participants":41},"route":"/key-papers/paper-hargrave-dabrafenib-trametinib-paediatric-hgg-jco-2023/","neighbours":{"cancer":[{"id":"paediatric-high-grade-glioma","kind":"cancer","name":"Paediatric high-grade glioma (excluding diffuse midline glioma)","route":"/cancers/paediatric-high-grade-glioma/"}],"drug":[{"id":"dabrafenib","kind":"drug","name":"Dabrafenib","route":"/drugs/dabrafenib/"},{"id":"trametinib","kind":"drug","name":"Trametinib","route":"/drugs/trametinib/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}