Bevacizumab Monotherapy Reduces Radiation-induced Brain Necrosis in Nasopharyngeal Carcinoma Patients: A Randomized Controlled Trial

Abstract

Studies have shown that addition of bevacizumab to corticosteroids improves outcome against radiation-induced brain necrosis (RN). Here, we aimed to evaluate the effectiveness and safety of bevacizumab monotherapy on RN in nasopharyngeal carcinoma (NPC) patients. In this multicenter open-label study, patients with RN were randomly assigned (1:1) into a bevacizumab group (5mg/kg intravenously every 2weeks, for 4 cycles) or a corticosteroid group (methylprednisolone 500mg/day intravenously for 3 consecutive days and then gradually tapered, followed by 10mg/day oral prednisone, for 2months in total). Magnetic resonance imaging (MRI) was performed pre- and post-treatment to define the radiographic response. The primary outcome was a 2-month response rate as determined by MRI and clinical symptoms. All of the patients were followed up with for 6months. The trial was registered at www.clinicaltrials.gov (NCT01621880). Of 121 patients screened, 112 patients met the entry criteria. Thirty-eight (65.5%) patients in the bevacizumab group showed response, which was significantly higher than that in the corticosteroid group (65.5% vs 31.5%, P<.001). The mean percentage decrease in RN volume seen on T1 post-gadolinium and T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI was 25.5% and 51.8%, respectively, in the bevacizumab group, versus 5.0% and 19.3%, respectively, in the corticosteroid group. Moreover, 36 patients (62.1%) on bevacizumab and 23 patients (42.6%) on corticosteroids demonstrated clinical improvement (P=.039). During the 6-month follow up, fourteen patients on bevacizumab and 13 patients on corticosteroids showed RN recurrence. The most frequent adverse event in the bevacizumab group was hypertension (20.6%). Our study indicate that compared with corticosteroids, bevacizumab offers improved symptomatic relief and radiographic response.