CTIM-12. RANDOMIZED PHASE 2 STUDY OF NIVOLUMAB (NIVO) PLUS EITHER STANDARD OR REDUCED DOSE BEVACIZUMAB (BEV) IN RECURRENT GLIOBLASTOMA (rGBM). (9th November 2020)

• Record Type: Journal Article
• Authors: Ahluwalia, Manmeet; Peereboom, David; Rauf, Yasmeen; Lathia, Justin; Alban, Tyler; Schilero, Cathy; Ciolfi, Marci; LaForest-Roys, Corey; Nayak, Lakshmi; Lee, Eudocia; Wen, Patrick; Reardon, David
• Is Part Of: Neuro-oncology. Volume 22(2020)Supplement 2
• Page Start: ii35
• Page End: ii35
• Publication Date: 2020-11-09
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa215.146
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: 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.