P17.24.B BEVACIZUMAB VERSUS DEXAMETHASONE AS FIRST-LINE TREATMENT FOR SYMPTOMATIC CEREBRAL RADIATION NECROSIS AFTER RADIATION OF HIGH GRADE GLIOMA OR BRAIN METASTASES: A RANDOMIZED CLINICAL TRIAL

Abstract BACKGROUND Cerebral radiation necrosis (CRN) is a serious late complication of high-dose radiation therapy for brain metastases (BM) or gliomas, potentially leading to significant neurological symptoms and impaired quality of life (QoL). First-line therapy with corticosteroids (e.g., dexamethasone) frequently causes side effects, may lead to refractory neurological symptoms in some cases, and can interfere with immunotherapy. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF) has shown promise as a second-line treatment for steroid-refractory sCRN. However, the optimal first-line treatment for symptomatic CRN (sCRN) remains unclear. MATERIAL AND METHODS The BRAINS study is a multicenter, randomized clinical trial evaluating the clinical efficacy and cost-effectiveness of bevacizumab versus dexamethasone as first-line therapy for sCRN in two parallel patient cohorts: those with high-grade glioma (HGG) and BM. Eligible patients are adults with sCRN ≥ 3 months post-stereotactic radiotherapy of BM or focal radiotherapy for HGG, a Karnofsky Performance Status (KPS) score ≤ 90, and a decline of ≥2 points in at least one domain of the Neurologic Assessment in Neuro-Oncology (NANO) scale. Patients who have received prior treatment with bevacizumab within the last 6 months, require decompressive surgery, have any comorbidity that contraindicates study medication, or have a life expectancy of less than 3 months are ineligible. A total of 408 patients will be randomized in a 1: 1 ratio to receive either: 1) intravenous bevacizumab (flat dose 600 mg every three weeks for four cycles), or 2) daily oral dexamethasone, tapered over 12 weeks. Dexamethasone may be used concurrently with bevacizumab if clinically indicated. Follow-up of patients will be 2 years. The primary endpoint is a favorable clinical response at 12 weeks, defined as dexamethasone use of ≤1.5mg/day combined with either ≥ 10 points improvement in KPS with at least stable NANO or ≥ 2 points improvement in NANO with at least stable KPS. Key secondary endpoints are: QoL, cognitive function, epileptic seizure control, toxicity, recurrence of sCRN, and cost-effectiveness. The first patients will be enrolled from May 2025 onwards. Patient recruitment is expected to be completed by May 2028. The BRAINS study is funded by the Dutch Cancer Society (project no. 14642).