Abstract Details

Title Clinical Response of Recurrent Ganglioglioma with BRAF A598_T599insV Mutation to BRAF/MEK Inhibitors

Topic Neuro-oncology

Presentation(s) P9 - Poster Session 9 (11:45 AM-12:45 PM)

Poster/Presentation
Number 6-011

Objective We describe the first case of a ganglioglioma with a non-canonical activating BRAF A598_T599insV mutation in a patient with remarkable clinical response to BRAF/MEK inhibitor therapy.

Background Gangliogliomas are well-differentiated tumors associated with favorable prognosis and a five-year survival rate of 93%. Most gangliogliomas are benign low-grade tumors in young adults, but their heterogeneity may prompt tumor recurrence and progression. Tumors with BRAF mutations, most commonly occurring at the 600 codon, exhibit tumor proliferation via the MAPK pathway and effectively respond to approved targeted therapies like dual BRAF and MEK inhibition (BRAFi+MEKi). Conversely, non-V600E BRAF mutations have less predictive benefit and may exhibit tumor growth when treated with MAPK inhibition.

Our patient is a 19-year-old male with headaches found to have a posterior fossa ganglioglioma who underwent gross total resection. Within thirteen months, MRI demonstrated tumor recurrence. Next-generation sequencing revealed an exceedingly rare BRAF A598_T599insV mutation (class IIa). We treated the patient with Dabrafenib/Trametinib based on two metastatic melanoma case reports. The patient initially experienced a febrile reaction with nausea and vomiting that resolved with a drug holiday. Three months after treatment reinitiation, MRI demonstrated a marked decrease (>50%) of the tumor. The patient continues on Dabrafenib/Trametinib for sixteen months to date. Herein, we describe the first reported patient with a BRAF A598_T599insV mutated ganglioglioma exhibiting a durable response to BRAFi+MEKi.

Design/Methods Not Applicable.

Results Not Applicable.

Conclusions Our patient treated with BRAFi+MEKi demonstrated a moderate and durable response despite presenting with a non-V600E BRAF mutation. This case highlights a therapeutic option for recurrent gangliogliomas and other tumors harboring the BRAF A598_T599insV mutation. Further exploration of type 2 pan-RAF inhibitors and novel MEK-targeting therapies are needed to optimize treatments for cancers with non-V600E BRAF mutations. Overall, this case emphasizes the potential benefit of BRAFi+MEKi and importance of ongoing therapeutic development for rare BRAF mutations.

Authors/Disclosures
Jeremy G. Reynoso PRESENTER	Mr. Reynoso has nothing to disclose.
Denaly Chen, MD	Dr. Chen has nothing to disclose.
Frances E. Chow, MD (UCLA Neuro-Oncology Program)	Dr. Chow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novocure. Dr. Chow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Chow has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Chow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Servier.

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