Background: Trials with anti-PD1 in rGBM have shown limited efficacy. VEGF is highly upregulated proangiogenic growth factor in GBM contributing 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 may be a promising approach in rGBM.
Methods: 90 patients with first-recurrent GBM were randomized (1:1) to nivolumab (240 mg IV Q2 weeks) and bevacizumab at standard (10 mg/kg; Arm A) or low dose (3 mg/kg; Arm B) IV Q2 weeks. Eligibility also required KPS≥ 70% and dexamethasone ≤ 4 mg/day. Stratification included extent of resection, age, performance status and MGMT methylation status. Single cell RNA sequencing with CITE-seq was used to analyze blood samples from pre- and 8 weeks post-treatment among 8 responders and 8 non-responders.
Results: 90 patients were enrolled (May 2018- Jan 2020) and median follow-up is 7.5 months. Characteristics in 2 arms were comparable. Median age was 60.5 years (range 27-86), median KPS was 80. 35 patients were MGMT methylated, 53 unmethylated and 2 indeterminate. Estimated progression free survival (PFS) and median overall survival (OS) in arm A are 6.13 and 10.85 months and 4.59 and 9.61 months in Arm B, respectively. Single cell RNA sequencing with CITE-seq was used to analyze blood samples from 16 patients, baseline and 8 weeks post treatment. Standard dose bevacizumab treated patients had decreased myeloid derived suppressor cells and an inflammatory response gene signature at 8 weeks. Most frequent toxicities included fatigue (52.8%), headache (32.6%), diarrhea (31.5%), proteinuria (25.8) and hypertension (23.6%). Toxicity was comparable between 2 arms, except hypertension was more common in arm A.
Conclusions: PFS and OS rates appear similar for nivolumab with either standard or low-dose bevacizumab compared to historical benchmarks of bevacizumab monotherapy. Ongoing response evaluation and immunocorrelative data will be presented.