Vol.:(0123456789) 1 3
J Neurooncol
DOI 10.1007/s11060-017-2477-x
TOPIC REVIEW
The role of bevacizumab in the treatment of glioblastoma
Roberto Jose Diaz
1
· Sheikh Ali
2
· Mehreen Gull Qadir
3
· Macarena I. De La Fuente
4
·
Michael E. Ivan
5
· Ricardo J. Komotar
5
Received: 11 October 2016 / Accepted: 15 May 2017
© Springer Science+Business Media New York 2017
additional beneft reported to date in health-related quality
of life with the use of bevacizumab, although it may reduce
steroid requirements. On average there is one side-efect
event per patient and 74% of these events are grade 3 toxic-
ity or higher. Further studies investigating the role of beva-
cizumab in combination with cytotoxic agents at recurrence
are awaited.
Keywords Avastin · Bevacizumab · VEGF ·
Glioblastoma · Chemotherapy · Survival
Introduction
Glioblastoma (GBM) is the most common malignant pri-
mary brain tumor in adults. Despite advancements in
GBM treatment, such as the Stupp protocol,[1] it remains
an incurable disease. While an efective medical therapy
remains elusive, surgical resection of recurrent tumor in a
selected group of patients appears benefcial [2]. Multiple
adjuvant therapies have been proposed at the time of GBM
recurrence including cytotoxic chemotherapy, angiogenesis
inhibitors, or immunotherapy [3]. The histology of GBM
is characterized by marked microvascular proliferation and
disruption of the blood brain barrier, which results in con-
trast enhancement on MRI. This is associated with overex-
pression of the vascular endothelial growth factor (VEGF-
A) [4]. Bevacizumab is an IgG1 humanized monoclonal
antibody that neutralizes the efect of VEGF-A [2]. The
FDA has approved bevacizumab for use in the treatment of
multiple cancers including colon (2004), lung (2006), kid-
ney (2009), and cervix (2014) cancers. In 2009, the FDA
approved the use of bevacizumab in treating adult patients
diagnosed with recurrent GBM based on the success of
two Phase 2 clinical trials [5, 6]. Subsequent clinical use of
Abstract Bevacizumab has been used in patients with
GBM as a salvage therapy since its approval in the United
States for recurrent GBM in 2009. In order to review the
therapeutic efect of bevacizumab in the primary and recur-
rent clinical setting we have performed a systematic analy-
sis of data from the published literature. Weighted median
progression free survival and overall survival were calcu-
lated and compared to standard therapy or other experi-
mental therapies. A qualitative analysis of the limited stud-
ies on health related quality of life and efects on steroid
requirements was also undertaken. We found that the avail-
able literature supports the use of bevacizumab for prolong-
ing PFS and OS in the recurrent setting either alone or in
combination with a cytotoxic agent (P < 0.05), but does not
support its use in the primary setting (P > 0.05). The sur-
vival advantage of bevacizumab compared to experimental
therapy at recurrence is limited to 4 months. There is no
Electronic supplementary material The online version of this
article (doi:10.1007/s11060-017-2477-x) contains supplementary
material, which is available to authorized users.
* Roberto Jose Diaz
roberto.diaz@mcgill.ca
1
Department of Neurology and Neurosurgery, Montreal
Neurological Institute and Hospital, McGill University, 3801
Rue University, Montreal H3A 2B4, QC, Canada
2
College of Osteopathic Medicine, Nova Southeastern
University, Fort Lauderdale, FL, USA
3
Department of Biological Sciences, Florida International
University, Miami, FL, USA
4
Department of Neurology, University of Miami Miller
School of Medicine, Miami, FL, USA
5
Department of Neurological Surgery, University of Miami
Miller School of Medicine, Miami, FL, USA