Bevacizumab and Glioblastoma: Past, Present, and Future Directions

  title={Bevacizumab and Glioblastoma: Past, Present, and Future Directions},
  author={Michelle M. Kim and Yoshie Umemura and Denise Leung},
  journal={The Cancer Journal},
Abstract Glioblastoma (GBM) is the most common and lethal intracranial malignancy, with few advances in treatment over the last several decades. Much excitement surrounded the initial approval for bevacizumab for recurrent GBM, given the marked radiographic responses and improvement in progression-free survival observed in early studies. However, phase III studies have failed to demonstrate an overall survival advantage with the use of this agent. An overview of the mechanism of action and… 

New Directions in the Therapy of Glioblastoma

The current state of knowledge on novel targeted therapies in glioblastoma is described, including BRAF and MEK inhibition are more advantageous than BRAF inhibitor monotherapy and mTOR inhibitors (especially paxalisib) may be considered a particularly important group.

Recent Advances in Oncolytic Virotherapy and Immunotherapy for Glioblastoma: A Glimmer of Hope in the Search for an Effective Therapy?

To date, no targeted drugs, antibodies or combinations of chemotherapeutics have been demonstrated to be more efficient than temozolomide, or to increase efficacy of standard therapy (surgery,

Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity

Using the invasion spectrum of a tumor sample is a novel tool to distinguish between histological subtypes, specifying the tumor grades or different prognostic groups, and these are crucial steps towards personalized oncotherapy.

Immunotherapy for gliomas: shedding light on progress in preclinical and clinical development

The authors discuss immunotherapeutic strategies for glioma in phase-I/II clinical trials and illuminate their mechanisms of action, limitations, and key challenges, and examine promising approaches under preclinical development.

Temporal Trends in Glioblastoma Survival

After a period of progressive improvement in GBM survival between 2000 and 2011, survival plateaued and subsequent advances since 2011 have not yet been translated to improved survival on the population-level as of 2017.

Changes in the tumor microenvironment and treatment outcome in glioblastoma: A pilot study

Differences in the TME in respect of T-cell population, M1 and M2 macrophage polarization status, and MDSC population following different treatments in a syngeneic model of GBM showed that changes in theTME-associated cells were dependent on the therapeutic agents and the T ME-targeting therapy improved the survival of the GBM bearing animals.

Current perspectives on diffuse midline glioma and a different role for the immune microenvironment compared to glioblastoma

Insight is provided into the current status of DMG research, the knowledge of the immune microenvironment in DMG and GBM, and recent findings and therapeutic opportunities surrounding the TAM–glioma crosstalk are assessed.

Changes in the tumor microenvironment and outcome for TME-targeting therapy in glioblastoma: A pilot study

Differences in the TME in respect of T-cell population, M1 and M2 macrophage polarization status, and MDSC population following different treatments in a syngeneic model of GBM showed that changes in theTME-associated cells were dependent on the therapeutic agents, and the T ME-targeting therapy improved the survival of the GBM bearing animals.



Bevacizumab and radiotherapy for the treatment of glioblastoma: brothers in arms or unholy alliance?

This review will give insights into current concepts, limitations, and controversies regarding the molecular mechanisms and the clinical benefits of bevacizumab treatment in combination with radio(chemo)therapy - particularly in face of the results of recent phase III trials, which failed to demonstrate convincing improvements in overall survival (OS).

Bevacizumab for glioblastoma: current indications, surgical implications, and future directions.

Clinical results with bevacizumab for glioblastoma treatment to date, ongoing trials designed to address unanswered questions, current clinical indications based on existing data, neurosurgical implications of bevacszumab use in patients with gliOBlastoma, the current scientific understanding of the tumor response to short- and long-term bevazquezumab treatment, and future studies that will need to be undertaken to enable this treatment to fulfill its therapeutic promise.

Deferred use of bevacizumab for recurrent glioblastoma is not associated with diminished efficacy.

Analysis of treatment continuation rates indicated that the number of patients unable to undergo further treatments is modest, and that Patients unable to tolerate BV delay can be identified by age ≥ 60 years and low extent of resection.

Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma.

Adding carboplatin resulted in more toxicity without additional clinical benefit, and clinical outcomes in patients with recurrent GBM treated with bevacizumab were inferior to those in previously reported studies.

Identification of Patients with Recurrent Glioblastoma Who May Benefit from Combined Bevacizumab and CCNU Therapy: A Report from the BELOB Trial.

It is demonstrated that tumors assigned to the IGS-18 or "classical" subtype and treated with beva+CCNU showed a significant benefit in progression-free survival and a trend toward benefit in overall survival, whereas other subtypes did not exhibit such benefit.

Recurrent high-grade glioma treated with bevacizumab: prognostic value of MGMT methylation, EGFR status and pretreatment MRI in determining response and survival

The extent of edema relative to enhancing area may have a prognostic role specific to Grade III HGG, and area of enhancing tumor at baseline can stratify survival in patients with recurrent HGG treated with bevacizumab.

Improved tumor oxygenation and survival in glioblastoma patients who show increased blood perfusion after cediranib and chemoradiation

It is demonstrated that improved perfusion occurs only in a subset of patients in cediranib-containing regimens, and is associated with improved overall survival in these nGBM patients, and these results may provide new insight into the selection of glioblastoma patients most likely to benefit from anti-VEGF treatments.

Bevacizumab and dose-intense temozolomide in recurrent high-grade glioma.

  • J. VerhoeffC. Lavini D. Richel
  • Medicine, Biology
    Annals of oncology : official journal of the European Society for Medical Oncology
  • 2010
Treatment with bevacizumab and TMZ is feasible and well tolerated but did not improve PFS6 and median OS.

Lomustine and Bevacizumab in Progressive Glioblastoma

Despite somewhat prolonged progression‐free survival, treatment with lomustine plus bevacizumab did not confer a survival advantage over treatment with LOMustine alone in patients with progressive glioblastoma.

Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial.

  • T. SandmannR. Bourgon C. Bais
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2015
Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneural glioblastoma may derive an OS benefit from first-line bevacizumab treatment.