PATH-34. Assessment of BRAF alterations and recommended treatments in CNS tumors with BRAF alterations

Abstract BACKGROUND Comprehensive genomic profiling (CGP) has been reimbursed in Japan since June 2019, enabling treatment decisions based on genetic alterations. However, only 10–15% of patients receive genomically matched therapy, and its clinical utility remains limited. Our study aimed to assess the CGP-guided therapy for CNS tumors with BRAF alterations eligible for BRAF/MEK inhibitors using data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT). METHODS We reviewed CNS tumor cases with BRAF substitutions, indels, rearrangements, or atypical variants registered in C-CAT between 2016 and April 2025. We analyzed the types of BRAF alterations, expert panel (EP) recommendations, actually received treatment and reasons for not receiving recommended therapy. Oncogenicity was assessed using OncoKB. RESULTS We analyzed 267 cases harboring BRAF alterations. BRAF alterations included V600E (59.6%), fusions (27.7%), and other oncogenic mutations (12.7%). EP recommended matched therapy in 169 cases (63.3%), and 55 (20.6%) actually received. Among 70 cases with documented reasons for not receiving recommended therapy, 24 (34.3%) received other treatment, 20 (28.6%) were ineligible for trials and 8 (11.4%) were excluded due to poor performance status and declined treatment, respectively. CONCLUSION EP-recommended treatment was proposed in 63% of CNS tumors with BRAF alterations, but only 20% of patients received the recommended therapy. Major reasons for not receiving recommended therapy included trial ineligibility and poor general condition or patients decline.