MODL-01. SAFETY IN CONCOMITANT USE OF MEK AND BRAF INHIBITORS WITH BEVACIZUMAB

BACKGROUND: MEK and BRAF inhibitors are increasingly common treatments for pediatric nervous system tumors. While effective in blocking Ras/Raf/MEK/ERK pathway activation driving tumor progression, the side effect profile differs from traditional cytotoxic chemotherapies. Little data exists on overlapping toxicities with other targeted agents like bevacizumab despite their potential combined therapeutic benefit. METHODS: A retrospective review of patients treated with MEK +/- BRAF inhibitors and bevacizumab from 2015–2019 was conducted. Data collected included demographics, tumor type, neurofibromatosis status, treatment duration, reason for concurrent treatment, and toxicities. RESULTS: Fifteen patients aged 3–24 years old (median age 14 years) were identified. Diagnoses included five high-grade gliomas, four low-grade gliomas, four benign nerve sheath tumors, and one ependymoma. Nearly half (46.7%) were positive for neurofibromatosis type 1. Three patients were treated with a BRAF + MEK inhibitor and twelve were treated with a MEK inhibitor combined with bevacizumab. Duration of treatment ranged from 16–420 days (median 119 days). Reasons for concomitant therapy included progressive disease with neurologic decline (46.7%), painful benign nerve sheath tumors (26.7%), and visual loss with optic pathway gliomas (26.7%). Toxicities while on concurrent therapy included one episode of grade 1 left ventricular dysfunction, one grade 1 bleeding episode, and one grade 2 wound complication. There were no episodes of hypertension, thrombosis, GI perforations, or cytopenias. CONCLUSIONS: Our preliminary experience suggests bevacizumab in combination with MEK and BRAF inhibitors can be used safely across a variety of pediatric nervous tumors. Larger studies are needed to confirm these findings.