Bevacizumab does not extend lives of newly diagnosed glioblastoma patients

March 6, 2014 by Nancy Fredricks

(Medical Xpress)—Results from a randomized, phase 3 clinical trial conducted by the Radiation Therapy Oncology Group (RTOG) have shown that adding bevacizumab, a drug that inhibits the growth of blood vessels, to the treatment of glioblastoma (GBM) does not improve patient survival.

Results appear in the Feb. 20, 2014, issue of the New England Journal of Medicine. Arnab Chakravarti, MD, chair of at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital & Richard J. Solove Research Institute (OSUCCC – James) served as national translational research study chair of the international RTOG study. Mark Gilbert, MD, a professor of neuro-oncology with the University of Texas MD Anderson Cancer Center, served as the clinical principal investigator of the overall study.

GBM is the most common form of adult brain cancer. It has an average survival of less than 16 months, and few patients live beyond five years. The growth of new is a characteristic of GBM development, and this growth is stimulated by a substance released by GBM cells called vascular endothelial growth factor A (VEGF-A).

Bevacizumab is an antibody-based drug that targets VEGF-A to block the growth of tumor-derived blood vessels. Clinical trials evaluating the addition of bevacizumab to standard treatment for recurrent GBM demonstrated clinical benefit and led to the drug's Food and Drug Administration approval in 2009 as a second-line therapy for GBM as a single agent.

In this new study, researchers sought to determine if administering bevacizumab as part of first-line treatment improved survival among GBM patients. An unprecedented 621 adult study participants were enrolled to the multicenter trial and randomized into one of two study arms, with treating physicians blinded to treatment assignment. All participants consented to provide tumor tissue and blood samples for future research as part of the study.

Study participants were assigned equally across study arms using DNA-methylation status as a predictor of patient response to therapy. Previous studies have suggested that patients with methylated tumor promoters do significantly better than those with unmethylated tumor promoters. Because of this, researchers hypothesized that patients with a worse prognosis—as determined by their tumor marker—would do better if they received bevacizumab as a first-line treatment.

All participants were given standard-of-care consisting of radiation therapy and daily temozolomide chemotherapy. Starting at week four of and continuing every two weeks until disease progression, several treatment-related toxicities occurred or completion of adjuvant chemotherapy, patients randomized to the experimental arm of the study received bevacizumab while the control group received a placebo.

Study design allowed researchers to compare risk and benefit of early versus late treatment. Authors report a median survival of 20.5 months, which revealed no statistical difference in overall survival between the two study arms and suggested no added benefit to giving bevacizumab is a first-line therapy in terms of survival.

"The results of this trial demonstrate that personalized care approaches are desperately needed for glioblastoma (GBM) patients and that a 'one glove fits all approach' may be less fruitful in the management of GBMs," says Chakravarti, principal investigator of the local arm of study, which enrolled about 10 patients to the study.

"Through careful molecular, genetic and epigenetic profiling, our teams within the RTOG and the Ohio State University Comprehensive Cancer Center are uncovering the underlying mechanisms that contribute to treatment resistance in these most devastating tumors," adds Chakravarti. "What we are beginning to understand is that GBMs are comprised of dozens—if not hundreds—of distinct molecular subtypes of tumors. Novel therapies such as must be personalized towards an individual's tumor versus being directed towards a broad histopathological class of tumors so that the appropriate patient population may benefit."

Explore further: Adding bevacizumab to initital glioblastoma treatment doesn't improve overall survival

Related Stories

Adding bevacizumab to initital glioblastoma treatment doesn't improve overall survival

February 19, 2014
Results of a randomized phase III clinical trial conducted by the Radiation Therapy Oncology Group determined that adding bevacizumab to initial treatment for glioblastoma did not improve patient overall survival or progression-free ...

Personalized vaccine for most lethal type of brain tumor shows promise

December 16, 2013
Patients with recurrent glioblastoma multiforme (GBM) treated with an experimental vaccine made from the patient's own resected tumor tissue showed an improved survival compared with historical patients who received the standard ...

Better treatment for brain cancer revealed by new molecular insights

July 9, 2012
Nearly a third of adults with the most common type of brain cancer develop recurrent, invasive tumors after being treated with a drug called bevacizumab. The molecular underpinnings behind these detrimental effects have now ...

Test helps target glioblastoma patients most likely to benefit from bevacizumab

June 2, 2013
A new test may help identify newly diagnosed glioblastoma patients more likely to benefit from bevacizumab (Avastin), according to new research from The University of Texas MD Anderson Cancer Center.

Study identifies possible new target for future brain cancer drugs

February 27, 2014
A molecule in cells that shuts down the expression of genes might be a promising target for new drugs designed to treat the most frequent and lethal form of brain cancer, according to a new study by researchers at The Ohio ...

Study reveal unexpected findings

February 28, 2014
Research on a deadly form of brain cancer co-authored by a physician at Barrow Neurological Institute at St. Joseph's Hospital and Medical Center has been published in the New England Journal of Medicine. The three-year research ...

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.