Efficacy of Treatments for Pediatric Patients With Relapsed/Refractory High-Grade Glioma: Results From a Systematic Review of the Literature

OBJECTIVES: Paediatric High-Grade Gliomas (HGG) are rare diseases and are associated with poor prognosis. Until recently, Temozolomide (TMZ) was the only treatment with an EU marketing authorisation for paediatric patients with recurrent HGG. Encouraging results were reported for the combination (D+T) dabrafenib (Finlee®) and trametinib (Spexotras®) in the single-arm, open-label component of the TADPOLE study, with subsequent EU approval in 2024. A systematic literature review (SLR) was conducted to identify studies reporting on the clinical efficacy/safety for treatments other than D+T in paediatric patients with relapsed/refractory BRAF V600 mutation-positive HGG. A secondary objective was to include a broader range of studies, irrespective of mutation.

METHODS: MEDLINE/PubMed, EMBASE, Cochrane Review databases and conference abstracts were searched. All the citations were screened by two independent reviewers, followed by a quality check by a third. Data from the included studies were extracted into a pre-defined data extraction grid. Studies were categorised according to the treatment evaluated (TMZ vs. other treatment) and history of TMZ.

RESULTS: The SLR did not identify any studies within the BRAF V600 mutation-positive paediatric patient population. Irrespective of mutation, a total of 27 studies were included, of which seven evaluated the use of TMZ. For studies evaluating TMZ, response rates ranged between 0–25%, median Progression-free survival (PFS) ranged between 2–3 months, and median overall survival (OS) ranged between 4–10 months. Of the 20 remaining studies that evaluated other treatments than TMZ, response rates ranged between 0–30%, median PFS ranged between 1–4 months, and median OS ranged between 3–9 months. Albeit in one study, the prior use of TMZ was not reported.

CONCLUSIONS: Children and young adults with relapsed/refractory HGG suffer from poor response, PFS and OS. There is therefore an unmet need for an effective therapy that delay progression and improve survival rates in patients with HGG.