Neoadjuvant Combination Treatment with Checkpoint Inhibitors, Chemotherapy, and BRAF/MEK Inhibitors for BRAFV600E Glioblastoma Results in Sustained Response: A Case Report

Radiation’s confounding and adverse effects on tumor microenvironment and normal brain could potentially be delayed by upfront combination treatment. We present a patient with newly diagnosed BRAFV600E-mutant, PD-L1-positive glioblastoma treated with off-label RAF/MEK inhibitors encorafenib/binimetinib after progressing on postoperative immune checkpoint blockade and temozolomide (no radiation administered: NCT03425292). Complete response occurred six months after adding encorafenib/binimetinib, and clinical benefit was sustained for over 20 months. Treatment was well-tolerated with manageable toxicities, with quality of life and cognitive function maintained throughout treatment. Adding encorafenib/binimetinib to immunotherapy and temozolomide conferred favorable and lasting efficacy for our BRAFV600E-mutant glioblastoma patient, justifying future studies.