BRAFV600E-mutated central nervous system tumors benefit from treatment with dabrafenib plus trametinib: Results from the Drug Rediscovery Protocol

INTRODUCTION: -mutated progressive or recurrent tumors of the central nervous system (CNS). The primary endpoints were clinical benefit (CB: confirmed complete or partial response [PR] or stable disease [SD] ≥ 16 weeks) and safety. RESULTS: Between January 2019 and May 2024, 30 patients started treatment, of whom 25 were evaluable for response after completing at least one full treatment cycle. CB was observed in 19 patients, including 11 with confirmed PR and eight with SD for ≥ 16 weeks, resulting in a CB-rate of 76% (95% CI, 54.9%-90.6%) and an objective response rate of 44% (95% CI, 24.4%-65.1%). After a median follow-up of 40.2 months, the median duration of response was 27.8 months (95% CI, 23.6 months-not reached). The median progression-free and overall survival were 18.1 months (95% CI, 8.4 months-not reached) and 32.3 months (95% CI, 22.0 months-not reached), respectively. No unexpected toxicities were observed. CONCLUSIONS: -mutated CNS-tumors, representing a valuable therapeutic option for these vulnerable patients.