Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Neurooncol. 2020 Feb;146(3):451-458. doi: 10.1007/s11060-019-03339-0. Epub 2020 Feb 4.
First-line bevacizumab (BEV) is now available as a treatment option for glioblastoma patients with severe clinical conditions in Japan. However, the survival benefits remain controversial. To elucidate these potential survival benefits, we retrospectively analyzed survival in glioblastoma patients receiving BEV.
We analyzed survival in 120 patients with IDH-wild type glioblastoma treated from 2002 to 2018. Overall survival (OS) was assessed in three treatment era subgroups [pre-temozolomide (TMZ), TMZ, and TMZ-BEV], and the correlations of prognostic factors with survival were evaluated.
An improvement in survival was observed after BEV approval (median OS in the pre-TMZ, TMZ, and TMZ-BEV eras: 14.6, 14.9, and 22.1 months, respectively). A Cox proportional hazards model identified extent of resection and MGMT methylation status as significant prognostic factors in the TMZ era; however, these factors were not significant in the TMZ-BEV era. In subgroup analyses, patients with MGMT methylation had improved OS after TMZ introduction (pre-TMZ vs. TMZ, 18.5 vs. 28.1 months; P = 0.13), and those without MGMT methylation had significantly increased OS after BEV approval (TMZ vs. TMZ-BEV, 12.2 vs. 16.7 months; P = 0.04).
Our findings imply that optional first-line administration of BEV can overcome the impact of conventional risk factors and prolong survival complementary to TMZ. The patient subgroups benefitting from TMZ and BEV did not seem to overlap, and stratification based on risk factors, including MGMT methylation status, might be effective for selecting patients in whom BEV should be preferentially used as a first-line therapy.
贝伐珠单抗(bevacizumab,BEV)现已成为日本重症胶质母细胞瘤患者的一线治疗选择。然而,其生存获益仍存在争议。为了阐明这些潜在的生存获益,我们回顾性分析了接受 BEV 治疗的胶质母细胞瘤患者的生存情况。
我们分析了 2002 年至 2018 年期间接受治疗的 120 例 IDH 野生型胶质母细胞瘤患者的生存情况。在三个治疗时代亚组[替莫唑胺(temozolomide,TMZ)前、TMZ 和 TMZ-BEV]中评估总生存期(overall survival,OS),并评估预后因素与生存的相关性。
BEV 获批后观察到生存改善(TMZ 前、TMZ 和 TMZ-BEV 时代的中位 OS 分别为 14.6、14.9 和 22.1 个月)。Cox 比例风险模型确定了切除范围和 MGMT 甲基化状态是 TMZ 时代的显著预后因素;然而,这些因素在 TMZ-BEV 时代并不显著。亚组分析显示,MGMT 甲基化患者在 TMZ 引入后 OS 改善(TMZ 前 vs. TMZ,18.5 与 28.1 个月;P=0.13),而无 MGMT 甲基化患者在 BEV 批准后 OS 显著增加(TMZ 与 TMZ-BEV,12.2 与 16.7 个月;P=0.04)。
我们的研究结果表明,一线选择使用 BEV 治疗可克服传统危险因素的影响,并与 TMZ 联合治疗延长生存。似乎受益于 TMZ 和 BEV 的患者亚组并不重叠,基于包括 MGMT 甲基化状态在内的危险因素分层可能有助于选择优先使用 BEV 作为一线治疗的患者。