Bevacizumab Safety in Patients with Central Nervous System Metastases
Bevacizumab Safety in Patients with Central Nervous System Metastases
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DOI：
10.1158/1078-0432.ccr-09-2439
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发表时间：
2010-01-01
影响因子：
11.5
通讯作者：
Rohr, Ulrich-Peter
中科院分区：
文献类型：
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作者：
Besse, Benjamin;Lasserre, Susan F.;Rohr, Ulrich-Peter
目的：1997年，1例肝细胞癌患者发生致死性脑出血后，将中枢神经系统（CNS）转移患者从贝伐珠单抗试验中排除。对贝伐单抗治疗的CNS转移患者的安全性信息进行了审查，以确定是否仍然有理由将这些患者从贝伐单抗治疗中排除。使用来自13项随机对照II/III期试验的数据集进行回顾性探索性分析（数据集A）、两项开放标签单臂安全性试验（数据集B）和两项包括接受治疗的CNS转移患者的前瞻性研究（数据集C）。在数据集A和B中，已知的CNS转移是排除标准; CNS转移患者在入组研究时存在未识别的CNS转移或在试验期间发生。结果：在数据集A中，8，443例患者中有187例（贝伐单抗组91例，非贝伐单抗组96例）发现了隐匿性脑转移。3例贝伐珠单抗治疗患者（3.3%）发生4级脑出血，而1例对照组患者（1.0%）发生5级脑出血。在数据集B中，4，382例患者中有321例最初存在隐匿性CNS转移，其中报告了2例1级和1例3级脑出血（0.9%）。在131例接受治疗的中枢神经系统转移患者在数据集C，贝伐单抗治疗的患者（0.8%）发展为2级脑hemorrhages.Conclusions：在这个选定的人群中，中枢神经系统转移患者发生脑出血的风险相似，独立于贝伐单抗治疗。因此，通常不应将此类晚期/转移性乳腺癌、非小细胞肺癌、肾癌和结直肠癌CNS转移患者从贝伐珠单抗治疗或临床试验中排除。临床癌症研究; 16（1）; 269-78。（C）2010年AACR。
Purpose: Patients with central nervous system (CNS) metastases were excluded from bevacizumab trials following a case of fatal cerebral hemorrhage in a patient with hepatocellular carcinoma in 1997. Safety information for bevacizumab-treated patients with CNS metastases was reviewed to determine whether general exclusion of these patients from bevacizumab treatment is still justified.Experimental Design: A retrospective exploratory analysis was conducted using datasets from 13 randomized controlled phase II/III trials (dataset A), two open-label single-arm safety trials (dataset B), and two prospective studies including patients with treated CNS metastases (dataset C). In datasets A and B, known CNS metastasis was an exclusion criterion; patients with CNS metastasis had unrecognized CNS metastases at study entry or developed them during the trial. All reported cerebral hemorrhage grades in patients with CNS metastases were quantified.Results: In dataset A, occult brain metastases were identified in 187 of 8,443 patients (91 in bevacizumab arms and 96 in non-bevacizumab arms). Three bevacizumab-treated patients (3.3%) developed grade 4 cerebral hemorrhage, whereas one control-arm patient (1.0%) developed grade 5 cerebral hemorrhage. In dataset B, 321 of 4,382 patients had initially occult CNS metastases, in whom two grade 1 and one grade 3 cerebral hemorrhage (0.9%) were reported. In 131 patients with treated CNS metastases in dataset C, one bevacizumab-treated patient (0.8%) developed grade 2 cerebral hemorrhage.Conclusions: In this selected population, patients with CNS metastases are at similar risk of developing cerebral hemorrhage, independent of bevacizumab therapy. Consequently, such patients with CNS metastases from advanced/metastatic breast cancer, non-small cell lung carcinoma, and renal and colorectal cancer should not be generally excluded from bevacizumab therapy or clinical trials. Clin Cancer Res; 16(1); 269-78. (C)2010 AACR.