Funakoshi Yusuke, Hata Nobuhiro, Kuga Daisuke, Hatae Ryusuke, Sangatsuda Yuhei, Fujioka Yutaka, Takigawa Kosuke, Mizoguchi Masahiro
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
Pharmaceuticals (Basel). 2020 Dec 16;13(12):470. doi: 10.3390/ph13120470.
Glioblastoma, the most common primary brain tumor in adults, has one of the most dismal prognoses in cancer. In 2009, bevacizumab was approved for recurrent glioblastoma in the USA. To evaluate the clinical impact of bevacizumab as a first-line drug for glioblastoma, two randomized clinical trials, AVAglio and RTOG 0825, were performed. Bevacizumab was found to improve progression-free survival (PFS) and was reported to be beneficial for maintaining patient performance status as an initial treatment. These outcomes led to bevacizumab approval in Japan in 2013 as an insurance-covered first-line drug for glioblastoma concurrently with its second-line application. However, prolongation of overall survival was not evinced in these clinical trials; hence, the clinical benefit of bevacizumab for newly diagnosed glioblastomas remains controversial. A recent meta-analysis of randomized controlled trials of bevacizumab combined with temozolomide in recurrent glioblastoma also showed an effect only on PFS, and the benefit of bevacizumab even for recurrent glioblastoma is controversial. Here, we discuss the clinical impact of bevacizumab for glioblastoma treatment by reviewing previous clinical trials and real-world evidence by focusing on Japanese experiences. Moreover, the efficacy and safety of bevacizumab are summarized, and we provide suggestions for updating the approaches and management of bevacizumab.
胶质母细胞瘤是成人中最常见的原发性脑肿瘤,其预后是癌症中最糟糕的之一。2009年,贝伐单抗在美国被批准用于复发性胶质母细胞瘤。为了评估贝伐单抗作为胶质母细胞瘤一线药物的临床影响,开展了两项随机临床试验,即AVAglio和RTOG 0825。结果发现贝伐单抗可改善无进展生存期(PFS),并且据报道作为初始治疗对维持患者的功能状态有益。这些结果促使贝伐单抗于2013年在日本获批,作为胶质母细胞瘤的保险覆盖一线药物,同时也用于二线治疗。然而,这些临床试验并未显示总生存期延长;因此,贝伐单抗对新诊断胶质母细胞瘤的临床益处仍存在争议。最近一项关于贝伐单抗联合替莫唑胺治疗复发性胶质母细胞瘤的随机对照试验的荟萃分析也仅显示对PFS有影响,而且贝伐单抗对复发性胶质母细胞瘤的益处也存在争议。在此,我们通过回顾以往的临床试验和基于日本经验的真实世界证据,来讨论贝伐单抗对胶质母细胞瘤治疗的临床影响。此外,总结了贝伐单抗的疗效和安全性,并为更新贝伐单抗的应用方法和管理提供建议。