Update on Chemotherapeutic Approaches and Management of Bevacizumab Usage for Glioblastoma

Abstract

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.

Volumetric study reveals the relationship between outcome and early radiographic response during bevacizumab-containing chemoradiotherapy for unresectable glioblastoma

“…Accordingly, there is no robust evidence supporting the efficacy of BEV treatment for nd-GBM; however, BEV has been approved in Japan as an insurance-covered first-line drug for GBM concurrently with its second-line application, considering the benefit of maintaining patient performance status [5]. Thereafter, Japanese institutes, including ours, have launched several real-world studies, which indicate the clinical benefits of optional first-line BEV for patients with severe clinical conditions [1,[6][7][8][9][10]. Practically, we selected first-line BEV for patients with unresectable GBM and accumulated the clinical data [11].…”

“…Glioblastoma (GBM) is one of the most common malignant brain tumors and has a poor prognosis. The current standard treatment for newly diagnosed GBM (nd-GBM) is maximal safe removal with concurrent temozolomide and radiation (TMZ-RT), followed by maintenance TMZ with, if possible, tumor-treating fields [ 1 ]. Despite such multimodal treatment, the median overall survival (OS) remains less than 2 years.…”

Multimodal Role of PACAP in Glioblastoma

“…A previous study demonstrated that BV was efficacious in patients with IDH1 wild type proneural glioblastoma [63], whereas it failed in some other treated patients [64]. Moreover, it has been reported that BV showed limited benefit on recurrent GBM, whereas it has no effects on the survival of patients with primary GBM [65,66]. This effect could be related to cells' epithelial-mesenchymal transition (EMT), responsible of drug-resistance and tumor relapse [67,68].…”

Small Extracellular Vesicles Released from Glioma Cells Under Hypoxic Conditions Induce Pericyte-phenotype Transition of Glioma Stem Cells.

“…Upon recurrence, tumors may not enhance, secondary to vascular normalization. In addition, other recent prospective comparisons of Bevacizumab with other chemotherapeutic regimens have shown no signi cant increase in overall survival (OS) (14,15). The mechanisms of Bevacizumab failure are likely complex and multifactorial.…”