Chinot Oliver L, Reardon David A
aAP-HM, Pole Neuroscience Cliniques, Service de Neuro-Oncologie, CHU Timone, Aix-Marseille University, Marseille, France bDepartment of Medical Oncology, Center for Neuro-Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Curr Opin Neurol. 2014 Dec;27(6):675-82. doi: 10.1097/WCO.0000000000000142.
A major recent clinical research focus for glioblastoma has been the therapeutic evaluation of antiangiogenic agents. Several vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors and a soluble decoy VEGF receptor have demonstrated nominal benefit among patients. In contrast, bevacizumab, a humanized VEGF monoclonal antibody, exhibits evidence of apparent antitumor benefit, although these data remain controversial. In this review, we summarize how results of clinical trials evaluating bevacizumab to date influence the future of this therapeutic for recurrent and newly diagnosed glioblastoma patients.
Recently reported, placebo-controlled phase III studies demonstrate a meaningful progression-free survival increment, but no overall survival benefit among newly diagnosed patients treated with bevacizumab. For unclear reasons, quality-of-life surveys from these studies revealed divergent results. Among recurrent patients, uncontrolled trials demonstrate improved overall radiographic response and progression-free survival rates, although the impact of bevacizumab on overall survival remains to be defined by an ongoing randomized phase III trial.
The role of bevacizumab for glioblastoma remains uncertain but will likely be strongly influenced by results of a randomized phase III study among recurrent patients as well as further investigation of gene expression biomarker profiles to identify newly diagnosed patients more likely to derive survival benefit.
胶质母细胞瘤近期主要的临床研究重点是抗血管生成药物的治疗评估。几种血管内皮生长因子(VEGF)受体酪氨酸激酶抑制剂和一种可溶性VEGF受体诱饵已在患者中显示出一定益处。相比之下,人源化VEGF单克隆抗体贝伐单抗虽有明显抗肿瘤益处的证据,但这些数据仍存在争议。在本综述中,我们总结了迄今为止评估贝伐单抗的临床试验结果如何影响该疗法在复发性和新诊断胶质母细胞瘤患者中的未来应用。
最近报道的安慰剂对照III期研究表明,在接受贝伐单抗治疗的新诊断患者中,无进展生存期有显著延长,但总生存期无获益。原因不明的是,这些研究中的生活质量调查结果不一。在复发性患者中,非对照试验显示总体影像学反应和无进展生存率有所改善,尽管贝伐单抗对总生存期的影响仍有待正在进行的随机III期试验来确定。
贝伐单抗在胶质母细胞瘤中的作用仍不确定,但可能会受到复发性患者随机III期研究结果以及进一步研究基因表达生物标志物谱以识别更可能从生存获益的新诊断患者的强烈影响。