FDA Drug Approval Summary: Bevacizumab (Avastin®) as Treatment of Recurrent Glioblastoma Multiforme
FDA Drug Approval Summary: Bevacizumab (Avastin®) as Treatment of Recurrent Glioblastoma Multiforme
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DOI：
10.1634/theoncologist.2009-0121
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发表时间：
2009-01-01
期刊：
影响因子：
5.8
通讯作者：
Pazdur, Richard
中科院分区：
文献类型：
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作者：
Cohen, Martin H.;Shen, Yuan Li;Pazdur, Richard
2009年5月5日，美国国务院宣布，S.美国食品和药物管理局批准加速贝伐单抗注射剂（Avastin（R）; Genentech，Inc.，South San弗朗西斯科，CA）作为单一药物用于既往治疗后疾病进展的多形性胶质母细胞瘤（GBM）患者。批准是基于持久的客观缓解（独立的放射学审查，皮质类固醇使用稳定或减少）。提交了两项评价贝伐珠单抗10 mg/kg每2周一次静脉输注的试验。一项试验还将患者随机分配至贝伐单抗加伊立替康治疗组。所有患者既往均接受过手术、放疗和替莫唑胺治疗。排除活动性脑出血患者。一项试验招募了78名独立确认的GBM患者。在25.9%（95%置信区间[CI]，17.0%-36.1%）的患者中观察到部分缓解。中位缓解持续时间为4.2个月（95% CI，3.0-5.7个月）。第二项试验招募了56名GBM患者。在19.6%（95% CI，10.9%-31.3%）的患者中观察到部分缓解。中位缓解持续时间为3.9个月（95% CI，2.4-17.4个月）。提供了第一项研究的安全性数据。最常报告的任何级别的贝伐珠单抗不良事件为感染、疲乏、头痛、高血压、鼻衄和腹泻。3-5级贝伐珠单抗相关不良事件包括出血/出血、中枢神经系统（CNS）出血、高血压、静脉和动脉血栓栓塞事件、伤口愈合并发症、蛋白尿、胃肠道穿孔和可逆性后部白质脑病。某些不良事件的归因（例如，CNS出血、伤口愈合并发症和血栓栓塞事件）与贝伐珠单抗、基础疾病或两者的相关性，由于是单组、非比较性研究设计，因此无法确定。肿瘤学家2009;14：1131-1138
On May 5, 2009, the U. S. Food and Drug Administration granted accelerated approval to bevacizumab injection (Avastin (R); Genentech, Inc., South San Francisco, CA) as a single agent for patients with glioblastoma multiforme (GBM) with progressive disease following prior therapy. The approval was based on durable objective responses (independent radiologic review with stable or decreasing corticosteroid use). Two trials evaluating bevacizumab, 10 mg/kg by i.v. infusion every 2 weeks, were submitted. One trial also randomized patients to bevacizumab plus irinotecan treatment. All patients had received prior surgery, radiotherapy, and temozolomide. Patients with active brain hemorrhage were excluded. One trial enrolled 78 independently confirmed GBM patients. Partial responses were observed in 25.9% (95% confidence interval [CI], 17.0%-36.1%) of the patients. The median response duration was 4.2 months (95% CI, 3.0-5.7 months). The second trial enrolled 56 GBM patients. Partial responses were observed in 19.6% (95% CI, 10.9%-31.3%) of the patients. The median response duration was 3.9 months (95% CI, 2.4-17.4 months). Safety data were provided for the first study. The most frequently reported bevacizumab adverse events of any grade were infection, fatigue, headache, hypertension, epistaxis, and diarrhea. Grade 3-5 bevacizumab-related adverse events included bleeding/hemorrhage, central nervous system (CNS) hemorrhage, hypertension, venous and arterial thromboembolic events, wound-healing complications, proteinuria, gastrointestinal perforation, and reversible posterior leukoencephalopathy. The attribution of certain adverse events (e.g., CNS hemorrhage, wound-healing complications, and thromboembolic events) to either bevacizumab, underlying disease, or both could not be determined because of the single-arm, noncomparative study design. The Oncologist 2009;14:1131-1138