Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
Ann Oncol. 2018 Jun 1;29(6):1431-1436. doi: 10.1093/annonc/mdy106.
The vascular endothelial growth factor antibody bevacizumab (Avastin®), received approval for the treatment of recurrent glioblastoma in many countries including the USA and Switzerland, but not the European Union, in 2009. Here, we explored the hypothesis that the approval of bevacizumab improved outcome with glioblastoma on a population level.
The prognostic significance of epidemiological, molecular genetic, and clinical data including treatment for glioblastoma patients diagnosed from 2010 to 2014 in the Canton of Zurich, Switzerland, was retrospectively analyzed using log-rank test and Cox proportional hazards models. Data were compared with data for the years 2005-2009.
In total, 310 glioblastoma patients were identified in the years 2010-2014. Median overall survival was 13.5 months for patients with known isocitrate dehydrogenase (IDH) wild-type (wt) (IDH1R132H-non-mutant) tumors (N = 248), compared with 11.3 months for IDH wt patients (P = 0.761) before (2005-2009). In the IDH wt cohort, bevacizumab use at any time increased from 19% in 2005-2009 to 49% in 2010-2014. Multivariate analysis did not identify bevacizumab exposure at any time to be associated with survival. Yet, upon the second-line treatment, baseline doses of corticosteroids were reduced by more than half in 83% of patients on bevacizumab compared with 48% of the patients treated with bevacizumab-free regimens (P = 0.007).
This epidemiological study of a small, but clinically well-annotated patient cohort fails to support the assumption that the strong increase of bevacizumab use since 2010 improved survival in glioblastoma although clinical benefit associated with decreased steroid use may have been achieved.
血管内皮生长因子抗体贝伐单抗（阿瓦斯汀®）于 2009 年在包括美国和瑞士在内的许多国家获得复发性胶质母细胞瘤的治疗批准，但在欧盟未获得批准。在这里，我们探讨了这样一种假设，即贝伐单抗的批准改善了人群水平上的胶质母细胞瘤的预后。
使用对数秩检验和 Cox 比例风险模型对 2010 年至 2014 年在瑞士苏黎世州诊断的胶质母细胞瘤患者的流行病学、分子遗传学和临床数据（包括治疗）的预后意义进行回顾性分析。将数据与 2005-2009 年的数据进行比较。
在 2010-2014 年期间，共确定了 310 名胶质母细胞瘤患者。已知异柠檬酸脱氢酶（IDH）野生型（wt）（IDH1R132H-非突变）肿瘤患者的中位总生存期为 13.5 个月（N=248），而 IDH wt 患者的中位总生存期为 11.3 个月（P=0.761）在 2005-2009 年之前。在 IDH wt 队列中，任何时间使用贝伐单抗的比例从 2005-2009 年的 19%增加到 2010-2014 年的 49%。多变量分析并未发现任何时间暴露于贝伐单抗与生存相关。然而，在二线治疗中，与贝伐单抗无治疗方案相比，83%的贝伐单抗治疗患者的基线剂量皮质类固醇降低了一半以上（P=0.007）。
尽管与减少使用皮质类固醇相关的临床获益可能已经实现，但这项对小但临床注释良好的患者队列的流行病学研究未能支持贝伐单抗使用量自 2010 年以来大幅增加改善胶质母细胞瘤患者生存的假设。
