Dr Abdelbaki on Second-Line Targeted Therapy in BRAF+ Pediatric Low-Grade Glioma

“The choice to decide on therapy depends on how patients tolerate initial therapies what [treatments] were used, and how long ago they occurred.”

Mohamed Abdelbaki, MD, a professor of pediatrics and director of the Pediatric Neuro-Oncology Program at the University of Washington School of Medicine, discussed treatment options for patients with pediatric low-grade glioma (pLGG) harboring BRAF V600E mutations or BRAF fusions in the second-line setting, and how data from the phase 2 FIREFLY-1 trial (NCT04775485) presented at the 2025 Society for Neuro-Oncology Annual Meeting has helped diversify treatment possibilities for patients.

Abdelbaki kicked off the conversation by laying out the options available for patients with newly diagnosed pLGG and future treatments that might become available to them. Abdelbaki noted how dabrafenib (Tafinlar) and trametinib (Mekinist) are part of the current standard of care for patients with pLGG harboring BRAF V600E mutations. However, a targeted therapy for patients with newly diagnosed pLGG with BRAF fusions has yet to be approved, Abdelbaki added. Abdelbaki said that despite the lack of targeted therapy options for this subgroup of patients with newly diagnosed pLGG, there are multiple ongoing clinical trials that are evaluating targeted therapies combined with chemotherapy.

Abdelbaki then moved into a discussion about targeted treatment options for patients with pLGG in the recurrent setting, specifically citing tovorafenib (Ojemda). In April 2024, tovorafenib was granted accelerated approval from the FDA for relapsed or refractory BRAF-positive pLGG, based on early results from the FIREFLY-1 trial that showed an objective response rate (ORR) of 52% in patients with pLGG harboring BRAF fusions (n = 64). Since then, updated results from the trial have shown that at a median follow-up of 40.6 months, patients with pLGG (n = 76) have achieved an ORR of 53%.

Factors like how well patients tolerate initial therapies, what kinds of treatments are used, and the timetable in which they occur are all crucial to Abdelbaki in determining which treatment to utilize for recurrent pLGG. In patients where dabrafenib and trametinib are well tolerated initially, restarting the therapy at recurrence of pLGG is an acceptable approach, according to Abdelbaki. However, Abdelbaki mentioned that in patients diagnosed with pLGG with BRAF V600E mutations who had not previously received dabrafenib and trametinib, considering tovorafenib in the recurrent setting might be an appropriate course of action. For patients diagnosed with pLGG with BRAF fusion in the recurrent setting, Abdelbaki stated that tovorafenib would be a favorable option, regardless of prior therapy.