CTIM-19. RANDOMIZED PHASE II OPEN-LABEL STUDY OF NIVOLUMAB PLUS STANDARD-DOSE BEVACIZUMAB VS NIVOLUMAB PLUS LOW-DOSE BEVACIZUMAB IN RECURRENT GLIOBLASTOMA (RGBM): FINAL REPORT

Abstract

Abstract BACKGROUND Anti-PD1 therapy alone in rGBM is of limited efficacy seen in three randomized trials. VEGF is upregulated proangiogenic growth-factor in GBM that contributes to tumor-associated immunosuppression. Preclinical data suggests a potential dose effect of anti-VEGF therapy on immunomodulation. Hence, a combination of anti-PD1 and anti-VEGF is promising approach. METHODS 90 patients with GBM at first recurrence were randomized (1:1) to nivolumab (240 mg IV Q2 weeks) with bevacizumab at standard (10 mg/kg; Arm A) or at low dose (3 mg/kg; Arm B) IV Q2 weeks. Stratification included extent of resection, age, performance-status, and MGMT methylation status. Progression-free survival (PFS) and overall survival (OS) were compared. RESULTS 90 patients (Median age 60.6 years, 67.8% male, median KPS 80) were enrolled between May 2018 and Jan 2020. Patients were followed in median 7.7 months (Range 0.7, 28.2). 35 patients were MGMT methylated and 53 patients were MGMT not hypermethylated and 2 were indeterminate. Overall survival was similar between arm A and arm B (1 year: 41.1 vs 37.7%, p = 0.14), while OS was better for arm A in age > 60 compared to arm B (At 1-year: 46.2% vs 23.8%; Median: 10.6 vs 5.9 months; P = 0.046). OS was not statistically different in the two arms for patients with age ≤ 60 years (At 1-year: 35.6% vs 56.4; Median 8.0 vs 12.4 months; P = 0.90). Most frequent toxicities ( >20%) included fatigue (45.6%), proteinuria (34.4 %), diarrhea (28.9%), hypertension (23.3%) and lipase increase (21.1%). Toxicities in grade 3-4 were hypertension (7.8%), fatigue (5.6) and other non-neurological toxicities including DVT, PE, infection, and abnormal liver function. CONCLUSIONS Overall PFS and OS rates appear similar for nivolumab with either standard or low-dose bevacizumab compared bevacizumab monotherapy. Nivolumab with standard bevacizumab benefits patients older than 60 years old. Biomarkers of response data will be presented.