R/R pLGG With a KIAA1549-BRAF Fusion Treated With Tovorafenib

This case focuses on the treatment of a pediatric low-grade glioma (pLGG) characterized by a KIAA1549-BRAF fusion, a common genetic alteration found in these tumors. The patient presented with relapsed or refractory disease after previous therapy, a scenario where standard treatment options are often limited or less effective. KIAA1549-BRAF fusions activate the MAPK signaling pathway but respond differently to targeted therapies compared to BRAF V600E mutations, necessitating distinct therapeutic approaches.

Tovorafenib, a selective type II pan-RAF inhibitor, was used as the treatment in this case. Unlike BRAF inhibitors such as dabrafenib or vemurafenib, which can paradoxically worsen tumors with BRAF fusions, tovorafenib has shown promise in targeting RAF-driven signaling regardless of mutation type. The patient received this therapy following disease progression on previous treatments. The rationale behind choosing tovorafenib lies in its ability to effectively inhibit signaling in tumors with BRAF fusions, without inducing paradoxical activation.

The clinical response to tovorafenib was favorable, with evidence of tumor stabilization or regression and manageable side effects. This aligns with emerging data supporting tovorafenib’s role in treating pLGG with BRAF fusions, especially in relapsed or refractory settings. Imaging surveillance was likely used to monitor tumor behavior throughout treatment. This case contributes to growing support for the use of molecularly targeted therapies tailored to the specific genetic landscape of pediatric gliomas. It emphasizes the importance of identifying BRAF fusion status early to guide appropriate therapy and avoid agents like first-generation BRAF inhibitors, which can be contraindicated in this context.