Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland.
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
J Cancer Res Clin Oncol. 2020 Mar;146(3):659-670. doi: 10.1007/s00432-019-03086-9. Epub 2019 Nov 21.
The use of alkylating chemotherapy versus bevacizumab for recurrent glioblastoma remains controversial. Here, we tested the hypothesis that the activity of alkylators, but not that of bevacizumab, would be associated with the O-methylguanine DNA methyltransferase (MGMT) promoter methylation status.
We analyzed a cohort of patients treated at centers of the German Glioma Network or the University Hospital Zurich with alkylating agent-based chemotherapy (n = 260) or bevacizumab without or with irinotecan (n = 84) for first recurrence of glioblastoma. Outcome was stratified for O-methylguanine DNA methyltransferase (MGMT) status and crossover to bevacizumab or alkylators at further progression.
Median post-recurrence survival-1 (PRS-1) for patients receiving alkylating agents at first recurrence was longer than with bevacizumab (11.1 versus 7.4 months, p < 0.001). The use of alkylators was associated with longer PRS-1 for patients with a methylated versus unmethylated MGMT promoter (p = 0.017). For patients receiving bevacizumab, PRS-1 was not different with or without MGMT promoter methylation. PRS-1 was longer in patients receiving alkylating chemotherapy compared to bevacizumab for patients with methylated (p < 0.001) or unmethylated MGMT promoter (p = 0.034). For patients with alkylators at first recurrence receiving bevacizumab at any further recurrence, PRS-1 was longer than in patients receiving bevacizumab first and alkylators thereafter (p = 0.002).
This study confirms limited value of bevacizumab in recurrent glioblastoma independent of MGMT status. Alkylating agents have activity in recurrent glioblastoma, especially in the context of MGMT promoter methylation.
在复发性胶质母细胞瘤中，使用烷化剂化疗与贝伐单抗相比仍存在争议。在这里，我们检验了这样一个假设，即烷化剂的活性而不是贝伐单抗的活性与 O-甲基鸟嘌呤 DNA 甲基转移酶（MGMT）启动子甲基化状态有关。
我们分析了在德国神经胶质瘤网络或苏黎世大学医院中心接受烷化剂为基础的化疗（n=260）或贝伐单抗（n=84）治疗复发性胶质母细胞瘤的患者队列。根据 O-甲基鸟嘌呤 DNA 甲基转移酶（MGMT）状态对患者进行分层，并根据进一步进展时的交叉治疗进行分层。
首次复发时接受烷化剂治疗的患者中位 post-recurrence survival-1（PRS-1）比接受贝伐单抗的患者更长（11.1 个月对 7.4 个月，p<0.001）。对于 MGMT 启动子甲基化的患者，使用烷化剂与更长的 PRS-1 相关（p=0.017）。对于接受贝伐单抗治疗的患者，MGMT 启动子甲基化与否，PRS-1 无差异。对于接受烷化剂化疗的患者，MGMT 启动子甲基化（p<0.001）或非甲基化（p=0.034）的患者，PRS-1 均长于接受贝伐单抗的患者。对于首次复发时接受烷化剂治疗并在任何进一步复发时接受贝伐单抗的患者，PRS-1 长于首次接受贝伐单抗治疗且随后接受烷化剂治疗的患者（p=0.002）。
本研究证实了贝伐单抗在复发性胶质母细胞瘤中的价值有限，与 MGMT 状态无关。烷化剂在复发性胶质母细胞瘤中有活性，尤其是在 MGMT 启动子甲基化的情况下。
