Schaub Christina, Schäfer Niklas, Mack Frederic, Stuplich Moritz, Kebir Sied, Niessen Michael, Tzaridis Theophilos, Banat Mohammed, Vatter Hartmut, Waha Andreas, Herrlinger Ulrich, Glas Martin
Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
Stem Cell Pathologies Group, Institute of Reconstructive Neurobiology, University of Bonn Medical Center, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.
J Cancer Res Clin Oncol. 2016 Aug;142(8):1825-9. doi: 10.1007/s00432-016-2187-3. Epub 2016 Jun 18.
The adequate second-line therapy of patients with glioblastoma (GBM) is a matter of ongoing debate. This particularly applies to patients with a non-methylated MGMT promotor who are known to have a poor response to alkylating chemotherapy. In some countries, antiangiogenic therapy with BEV is applied as second-line therapy, and in others nitrosourea therapy is second-line choice. It is an open question whether the delay of BEV to third-line therapy has a negative impact on survival.
A total of 61 adult patients (median age 56.9 years) with MGMT-non-methylated relapsed GBM treated with BEV (n = 45) or nitrosourea (n = 16) as second-line therapy were analyzed retrospectively and compared regarding progression-free survival (PFS) and overall survival (OS).
Patients treated with second-line BEV had longer median PFS (107 days, 95 % CI 80.7-133.2 days) than patients with second-line nitrosourea (52 days, 95 % CI 36.3-67.7 days, P = 0.011, logrank test). However, there was no significant difference in overall survival (BEV median 170 days, 95 % CI 87.2-252.8 days; nitrosourea median 256 days, 95 % CI 159.9-352.0 days, P = 0.468). PFS was similar after BEV third-line therapy (median 117 days, 95 % CI 23.6-210.4 days) as compared to second-line BEV therapy (median 107 days, 95 % CI 80.7-133.3 days, P = 0.584).
Our findings suggest that early treatment with BEV in patients with MGMT-non-methylated relapsed GBM is associated with a better PFS, but not with superior OS, possibly implicating that the early, i.e., second-line, use of BEV is not mandatory and BEV treatment may safely be delayed to third-line therapy in this subgroup of patients.
胶质母细胞瘤(GBM)患者合适的二线治疗方案一直存在争议。这尤其适用于O⁶-甲基鸟嘌呤-DNA甲基转移酶(MGMT)启动子未甲基化的患者,已知这类患者对烷化剂化疗反应较差。在一些国家,贝伐单抗(BEV)抗血管生成治疗被用作二线治疗,而在其他国家,亚硝基脲治疗是二线选择。BEV推迟至三线治疗是否会对生存产生负面影响仍是一个悬而未决的问题。
对61例成年患者(中位年龄56.9岁)进行回顾性分析,这些患者为MGMT未甲基化的复发性GBM,接受BEV(n = 45)或亚硝基脲(n = 16)作为二线治疗,并比较无进展生存期(PFS)和总生存期(OS)。
接受二线BEV治疗的患者中位PFS(107天,95%CI 80.7 - 133.2天)长于接受二线亚硝基脲治疗的患者(52天,95%CI 36.3 - 67.7天,P = 0.011,对数秩检验)。然而,总生存期无显著差异(BEV中位生存期170天,95%CI 87.2 - 252.8天;亚硝基脲中位生存期256天,95%CI 159.9 - 352.0天,P = 0.468)。与二线BEV治疗相比,BEV三线治疗后的PFS相似(中位117天,95%CI 23.6 - 210.4天)(中位107天,95%CI 80.7 - 133.3天,P = 0.584)。
我们的研究结果表明,MGMT未甲基化的复发性GBM患者早期使用BEV治疗与较好的PFS相关,但与更好的OS无关,这可能意味着在该亚组患者中,早期即二线使用BEV并非必要,BEV治疗可安全推迟至三线治疗。