贝伐珠单抗治疗新诊断的胶质母细胞瘤的随机试验。
A randomized trial of bevacizumab for newly diagnosed glioblastoma.
机构信息
From the University of Texas M.D. Anderson Cancer Center (M.R.G., T.S.A., J.S.W., P.D.B., I.W.T.-L., E.P.S., K.D.A.) and the University of Texas Health Science Center School of Nursing (T.S.A.), Houston; American College of Radiology (J.J.D., S.P., M.W.) and Thomas Jefferson University (M.W.-W.) - both in Philadelphia; the University of Chicago, Chicago (J.J.D.); Tel-Aviv Medical Center, Tel Aviv, Israel (D.T.B.); Cleveland Clinic, Cleveland (M.A.V.); the University of Utah, Salt Lake City (H.C.); Ohio State University, Columbus (A.C.); University of Wisconsin, Madison (R.J.); Mayo Clinic, Jacksonville, FL (K.A.J.); University of Virginia, Charlottesville (D.S.); Southeast Cancer Control Consortium, Winston-Salem, NC (V.W.S.); Barrow Neurologic Institute, Phoenix, AZ (D.G.B.); Emory University, Atlanta (W.J.C.); and the University of Maryland, Baltimore (M.P.M.).
出版信息
N Engl J Med. 2014 Feb 20;370(8):699-708. doi: 10.1056/NEJMoa1308573.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00884741.).
背景
替莫唑胺联合放疗后序贯替莫唑胺维持治疗是新诊断胶质母细胞瘤患者的标准治疗方案。贝伐珠单抗是人源化抗血管内皮生长因子 A 单克隆抗体，目前被批准用于复发性胶质母细胞瘤。新诊断的胶质母细胞瘤患者中添加贝伐珠单抗是否会改善生存情况尚不清楚。
方法
在这项随机、双盲、安慰剂对照的临床试验中，我们对经中心确诊的胶质母细胞瘤成年患者采用放疗（60Gy）和替莫唑胺每日治疗。在放疗第 4 周开始使用贝伐珠单抗或安慰剂，并继续进行最多 12 个周期的维持化疗。疾病进展时，揭示所分配的治疗方案，贝伐珠单抗治疗可以开始或继续进行。试验旨在检测添加贝伐珠单抗可使死亡风险降低 25%，疾病进展或死亡风险降低 30%，这是两个主要终点。
结果
共登记了 978 例患者，其中 637 例进行了随机分组。贝伐珠单抗组和安慰剂组的总生存期无显著差异（中位生存期分别为 15.7 个月和 16.1 个月；贝伐珠单抗组死亡风险比为 1.13）。贝伐珠单抗组的无进展生存期更长（10.7 个月 vs. 7.3 个月；疾病进展或死亡风险比为 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略有增加。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为频繁。
结论
在新诊断的胶质母细胞瘤患者中，一线使用贝伐珠单抗并未改善总体生存。无进展生存期延长，但未达到预设的改善目标。（由美国国立癌症研究所资助；ClinicalTrials.gov 编号，NCT00884741。）
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