A randomized trial of bevacizumab for newly diagnosed glioblastoma.
A randomized trial of bevacizumab for newly diagnosed glioblastoma.
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DOI：
10.1056/nejmoa1308573
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发表时间：
2014-02-20
期刊：
影响因子：
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通讯作者：
Mehta MP
中科院分区：
文献类型：
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作者：
Gilbert MR;Dignam JJ;Armstrong TS;Wefel JS;Blumenthal DT;Vogelbaum MA;Colman H;Chakravarti A;Pugh S;Won M;Jeraj R;Brown PD;Jaeckle KA;Schiff D;Stieber VW;Brachman DG;Werner-Wasik M;Tremont-Lukats IW;Sulman EP;Aldape KD;Curran WJ Jr;Mehta MP
替莫唑胺和放疗同时治疗，随后维持替莫唑胺是新诊断胶质母细胞瘤患者的标准治疗。贝伐单抗是一种抗血管内皮生长因子A的人源化单克隆抗体，目前已被批准用于治疗复发性胶质母细胞瘤。是否添加贝伐单抗将改善新诊断的胶质母细胞瘤患者的生存率尚不清楚。在这项随机、双盲、安慰剂对照试验中，我们对中心确诊的胶质母细胞瘤成人患者进行放疗（60戈伊）和每日替莫唑胺治疗。在放疗的第4周开始使用贝伐单抗或安慰剂治疗，并持续长达12个周期的维持化疗。在疾病进展时，显示分配的治疗，可以开始或继续贝伐珠单抗治疗。该试验旨在检测死亡风险降低25%和进展或死亡风险降低30%，这两个共同的主要终点，加上贝伐单抗。共登记了978例患者，其中637例接受了随机分组。贝伐珠单抗组和安慰剂组的总生存期没有显著差异（中位数分别为15.7和16.1个月;贝伐珠单抗组的死亡风险比为1.13）。贝伐单抗组的无进展生存期较长（10.7个月vs. 7.3个月;进展或死亡的风险比为0.79）。贝伐珠单抗组高血压、血栓栓塞事件、肠穿孔和中性粒细胞减少症的发生率适度增加。随着时间的推移，贝伐珠单抗组的症状负担增加，生活质量下降和神经认知功能下降更常见。一线使用贝伐单抗并不能提高新诊断胶质母细胞瘤患者的总生存率。无进展生存期延长，但未达到预定的改善目标。
Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known. In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary end points, with the addition of bevacizumab. A total of 978 patients were registered, and 637 underwent randomization. There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group (median, 15.7 and 16.1 months, respectively; hazard ratio for death in the bevacizumab group, 1.13). Progression-free survival was longer in the bevacizumab group (10.7 months vs. 7.3 months; hazard ratio for progression or death, 0.79). There were modest increases in rates of hypertension, thromboembolic events, intestinal perforation, and neutropenia in the bevacizumab group. Over time, an increased symptom burden, a worse quality of life, and a decline in neurocognitive function were more frequent in the bevacizumab group. First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. Progression-free survival was prolonged but did not reach the prespecified improvement target.