Neoadjuvant combination treatment with checkpoint inhibitors, chemotherapy, and BRAF/MEK inhibitors for BRAFV600E glioblastoma results in sustained response: A case report

Abstract

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 6 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.