BACKGROUND Targeting vascular endothelial growth factor (VEGF) alone does not improve overall survival (OS) in recurrent glioblastoma (rGBM). The angiopoiein (Ang)-TIE2 system may play a role in tumor survival under VEGF inhibition. We conducted a phase 2, double-blinded, placebo-controlled trial of bevacizumab plus trebananib (a novel Fc fusion protein that sequesters Ang1/Ang2) over bevacizumab alone in rGBM. METHODS Patients ≥18 years of age with a Karnofsky performance status ≥70 and GBM or variants in first or second relapse were randomized to bevacizumab 10 mg/kg every 2 weeks plus trebananib 15 mg/kg every week or bevacizumab plus placebo. The primary endpoint was 6-month progression-free survival (PFS). RESULTS After an initial 6-patient lead-in cohort confirmed the safety of combining bevacizumab and trebananib, 115 eligible patients were randomized to the control (n = 58) or experimental treatment (n = 57). In the control arm, 6-month PFS was 41.1%, median survival time was 11.5 months (95% CI, 8.4-14.2 months), median PFS was 4.8 months (95% CI, 3.8-7.1 months), and radiographic response (RR) was 5.9%. In the experimental arm, 6-month PFS was 22.6%, median survival time was 7.5 months (95% CI, 6.8-10.1 months), median PFS was 4.2 months (95% CI, 3.7-5.6 months), and RR was 4.2%. The rate of severe toxicities was not significantly different between arms. CONCLUSION The combination of bevacizumab and trebananib was well tolerated but did not significantly improve 6-month PFS rate, PFS, or OS for patients with rGBM over bevacizumab alone. The shorter PFS in the experimental arm with a hazard ratio of 1.51 (P = .04) suggests that the addition of trebananib to bevacizumab is detrimental.

中文翻译：

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NRG/RTOG 1122：贝伐珠单抗联合或不联合曲巴尼布治疗复发性胶质母细胞瘤或胶质肉瘤患者的 2 期、双盲、安慰剂对照研究。


背景单独靶向血管内皮生长因子（VEGF）并不能改善复发性胶质母细胞瘤（rGBM）的总生存期（OS）。血管生成素 (Ang)-TIE2 系统可能在 VEGF 抑制下的肿瘤存活中发挥作用。我们在 rGBM 中进行了贝伐珠单抗联合 Trebananib（一种新型 Fc 融合蛋白，隔离 Ang1/Ang2）与单独贝伐珠单抗的 2 期双盲安慰剂对照试验。方法 年龄≥18岁且卡氏体能状态≥70且首次或第二次复发有GBM或变异的患者被随机分配至贝伐单抗每两周10 mg/kg加每周15 mg/kg曲巴尼布或贝伐单抗加安慰剂。主要终点是 6 个月无进展生存期 (PFS)。结果 在最初的 6 名患者导入队列确认贝伐珠单抗和曲巴尼布联合治疗的安全性后，115 名符合条件的患者被随机分配至对照组 (n = 58) 或实验治疗组 (n = 57)。在对照组中，6 个月 PFS 为 41.1%，中位生存时间为 11.5 个月（95% CI，8.4-14.2 个月），中位 PFS 为 4.8 个月（95% CI，3.8-7.1 个月），放射学反应（ RR) 为 5.9%。在实验组中，6 个月 PFS 为 22.6%，中位生存时间为 7.5 个月（95% CI，6.8-10.1 个月），中位 PFS 为 4.2 个月（95% CI，3.7-5.6 个月），RR 为 4.2 %。各组之间的严重毒性发生率没有显着差异。结论 贝伐珠单抗和曲巴尼布联合治疗的耐受性良好，但与单独使用贝伐珠单抗相比，并未显着改善 rGBM 患者的 6 个月 PFS 率、PFS 或 OS。实验组的 PFS 较短，风险比为 1.51 (P = .04)，表明在贝伐珠单抗中添加曲巴尼布是有害的。