The combination of dabrafenib and trametinib can produce durable responses in pediatric patients with relapsed or refractory, BRAFV600-mutant high-grade glioma, according to research published in the Journal of Clinical Oncology.

In this phase 2 trial, the median duration of response with the combination was 22.2 months. The combination also produced “encouraging” survival results, according to researchers.

The trial ( Identifier: NCT02684058) included 41 patients with BRAFV600-mutant high-grade glioma. The most common histologies were glioblastoma multiforme (n=13), anaplastic pleomorphic xanthoastrocytoma (n=6), high-grade gliomas not otherwise specified (n=4), pleomorphic xanthoastrocytoma (n=4), and anaplastic astrocytoma (n=3).

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The median age at baseline was 13 (range, 2-17) years. About half of patients (48.8%) had grade 4 disease at diagnosis, and all patients had received prior treatment.

At a median follow-up of 25.1 months, 20 patients had discontinued dabrafenib and trametinib, most due to progressive disease (n=16). The median treatment duration was 16.7 (range, 0.3-39.6) months.

The overall response rate was 56.1% per independent review. Twelve patients had confirmed complete responses, and 11 patients had partial responses. The median duration of response was 22.2 months.

The median progression-free survival (PFS) was 9.0 months. The PFS rate was 66.8% at 6 months and 44.1% at 12 months.

Overall survival (OS) data were immature, but the median OS was 32.8 months. The OS rate was 76.3% at 12 months and 58.6% at 24 months.

All patients had at least 1 adverse event (AE), and 68.3% had grade 3 or higher AEs. The most common AEs of any grade were pyrexia (51.2%), headache (34.1%), and dry skin (31.7%). The most common grade 3 or higher AEs were headache (9.8%) and vomiting (4.9%).

The rate of treatment-related AEs was 82.9%, and the rate of grade 3 or higher treatment-related AEs was 26.8%. There were 3 fatal AEs, but none were related to treatment.

“These findings suggest that dabrafenib plus trametinib is a promising targeted therapy option for children and adolescents with relapsed/refractory BRAFV600-mutant HGG [high-grade glioma],” the researchers concluded.

Disclosures: This research was supported by Novartis Pharmaceuticals Corporation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Hargrave DR, Terashima K, Hara J, et al. Phase II trial of dabrafenib plus trametinib in relapsed/refractory BRAF V600–mutant pediatric high-grade glioma. J Clin Oncol. Published online August 29, 2023. doi:10.1200/JCO.23.00558