Use of Bevacizumab in recurrent glioblastoma: a scoping review and evidence map

Abstract

Background Glioblastoma (GBM) is the most malignant primary tumor in the brain, with poor prognosis and limited effective therapies. Although Bevacizumab (BEV) has shown promise in extending progression-free survival (PFS) treating GBM, there is no evidence for its ability to prolong overall survival (OS). Given the uncertainty surrounding BEV treatment strategies, we aimed to provide an evidence map associated with BEV therapy for recurrent GBM (rGBM). Methods PubMed, Embase, and the Cochrane Library were searched for the period from January 1, 1970, to March 1, 2022, for studies reporting the prognoses of patients with rGBM receiving BEV. The primary endpoints were overall survival (OS) and quality of life (QoL). The secondary endpoints were PFS, steroid use reduction, and risk of adverse effects. A scoping review and an evidence map were conducted to explore the optimal BEV treatment (including combination regimen, dosage, and window of opportunity). Results Patients with rGBM could gain benefits in PFS, palliative, and cognitive advantages from BEV treatment, although the OS benefits could not be verified with high-quality evidence. Furthermore, BEV combined therapy (especially with lomustine and radiotherapy) showed higher efficacy than BEV monotherapy in the survival of patients with rGBM. Specific molecular alterations (IDH mutation status) and clinical features (large tumor burden and double-positive sign) could predict better responses to BEV administration. A low dosage of BEV showed equal efficacy to the recommended dose, but the optimal opportunity window for BEV administration remains unclear. Conclusions Although OS benefits from BEV-containing regimens could not be verified in this scoping review, the PFS benefits and side effects control supported BEV application in rGBM. Combining BEV with novel treatments like tumor-treating field (TTF) and administration at first recurrence may optimize the therapeutic efficacy. rGBM with a low apparent diffusion coefficient (ADCL), large tumor burden, or IDH mutation is more likely to benefit from BEV treatment. High-quality studies are warranted to explore the combination modality and identify BEV-response subpopulations to maximize benefits.

HSPA5 and FGFR1 genes in the mesenchymal subtype of glioblastoma can improve a treatment efficacy

“…Temozolomide is currently known as an important chemotherapeutic for GBM treatment, but its limitations are highlighted by drug resistance (Chien et al 2021 ; Roh et al 2023 ; Teraiya et al 2023 ). Other treatment methods have been studied, including clinical trials for targeted therapies, such as bevacizumab, which targets VEGF (Fu et al 2023 ) and EGFR (erlotinib, lapatinib, and gefitinib) inhibitors that focus on EGFR , and PI3 K/AKT/mTOR inhibitors aimed at the PI3 K/AKT/mTOR signaling pathway (Pan and Magge 2020 ). However, the clinical efficacy of treatments targeting RTK exhibits limitations, regardless of their single or combined use (Qin et al 2021 ; Shao et al 2023 ).…”

Glioblastoma Therapy: Past, Present and Future

“…BEV is an anti-VEGF humanized monoclonal antibody that inhibits tumor-driven angiogenesis and may help in reducing patients’ immune suppression [ 234 , 372 , 373 ]. rGB with a low apparent diffusion coefficient, large tumor burden, or IDH mutation is more likely to benefit from BEV treatment [ 374 ]. BEV gained approval in 2009 for rGB treatment in the US and later in other countries, but BEV is not approved by the EMA as an SOC for rGB [ 375 , 376 ].…”

Molecular mechanisms of tumour development in glioblastoma: an emerging role for the circadian clock

“…Due to the positive significant correlation between an altered clock i.e., increased levels of BMAL1 in GBM, and VEGF levels 54 future studies may combine a VEGF inhibitor such as bevacizumab with a clock manipulator such as a CRY or REV-ERB agonist. Bevacizumab is approved for recurrent GBM, however only showed a positive effect on PFS, but not on OS 56 . The response to bevacizumab may be enhanced by this combination strategy.…”

“…As mentioned, POSTN was shown to be positively regulated by the CLOCK/BMAL1 complex 55 . Therefore, one explanation for the rather unsatisfactory response to the angiogenesis inhibitor bevacizumab in GBM 56 could be an upregulation of CLOCK/BMAL1 , as observed in the majority of human studies (see Table 1 ).…”