Case report: complete long-lasting response to multimodal third line treatment with neurosurgical resection, carmustine wafer implantation and dabrafenib plus trametinib in a BRAFV600E mutated high-grade glioma

Abstract

Dabrafenib plus trametinib is a promising new therapy for patients affected by BRAFV600E-mutant glioma, with high overall response and manageable toxicity. We described a complete and long-lasting response in a case of recurrent anaplastic pleomorphic xanthoastrocytoma CNS WHO-grade 3 BRAFV600E mutated. Due to very poor prognosis, there are a few described cases of high-grade glioma (HGG) patients treated with the combined target therapy as third-line treatment. The emergence of optimized sequencing strategies and targeted agents, including multimodal and systemic therapy with dabrafenib plus trametinib, will continue to broaden personalized therapy in HGG improving patient outcomes.

Keywords: BRAF inhibitors; BRAFV600E; MEK inhibitors; dabrafenib; high-grade glioma; pleomorphic xanthoastrocytoma; target therapy; trametinib.

Figure 1

Brain CT scan at diagnosis, August 2016 [(A): axial, (B): coronal, (C): sagittal].

Figure 2

Pleomorphic xanthoastrocytoma, CNS WHO grade 3, lesion composed of pleomorphic cells (A) and oligodendrocyte-like cells (C). Perivascular lymphocyte cuffing and granular bodies are present (A) as well as necrosis [(B), arrow] and mitoses [(C, D), arrows]. Hematoxylin and eosin stain (A-D); Original magnification: a-b 10 X, c 40 X, d 20 X.

Figure 3

Axial T1 contrast-enhanced brain MRI [(A): after first line therapy, January 2017; (B): at first progression, October 2017; (C): at second progression, presurgical, December 2018; (D): complete response during target therapy, December 2021; (E): persistence complete response one month after target therapy interruption, January 2024].