Exploring the Role of BRAF Inhibition in Primary CNS Malignancies

This OncLive News Network series explores the evolving role of BRAF inhibition in the management of primary central nervous system (CNS) malignancies. Experts Patrick Wen, MD and Karisa Schreck, MD, PhD review current standards of care, highlighting existing FDA-approved therapies and the clinical challenges posed by molecular diversity and treatment resistance. The discussion emphasizes how BRAF alterations—particularly V600 mutations—influence therapeutic decision-making and the incorporation of targeted inhibitors. A major focus is the emerging agent plixorafenib, a novel BRAF inhibitor designed to penetrate the CNS and target both class I and II mutations, potentially offering broader activity than existing drugs such as dabrafenib, encorafenib, vemurafenib, and tovorafenib. The faculty address safety considerations, common adverse events, and early findings from the FORTE basket trial, which is evaluating plixorafenib in recurrent or progressive BRAF-mutated CNS tumors. The series concludes with ongoing research efforts, novel molecular testing strategies, and priorities for future clinical trials.