Addition of Bevacizumab to the Treatment of Newly Diagnosed Glioblastoma Brain Tumors Does Not Extend Patients’ Lives  

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Posted: 2/18/2014

COLUMBUS, Ohio – 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 MedicineArnab Chakravarti, MD, chair of radiation oncology 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 blood vessels 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 radiation therapy 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 bevacizumab 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.”

This study was funded by the National Cancer Institute Fund (NCT00884741), other NCI grants (U10 CA21661 and U10 CA37422) and an unrestricted educational grant from Genentech, manufacturer of the drug Avastin (bevacizumab). Chakravarti has no financial interests in Genentech.

Institutions participating in this study include: Ohio State University, University of Texas Health Science Center, University of Chicago, Cleveland Clinic, University of Utah, University of Wisconsin, Mayo Clinic, University of Virginia, Southwest Cancer Control Consortium, Barrow Neurologic Institute, Thomas Jefferson University, Emory University and the University of Maryland.

About The OSUCCC-James

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only four centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 228-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S.News & World Report.

About The RTOG

The Radiation Therapy Oncology Group (RTOG) is administered by the American College of Radiology (ACR) and located in the ACR Center for Clinical Research in Philadelphia, PA. RTOG is a multi-institutional international clinical cooperative group funded primarily by National Cancer Institute grants CA21661, CA32115 and CA37422. RTOG has 40 years of experience in conducting clinical trials and is comprised of over 300 major research institutions in the United States, Canada and internationally. The group is accruing to 40 studies that involve radiation therapy alone or in conjunction with surgery and/or chemotherapeutic drugs or which investigate quality of life issues and their effects on patients with cancer.

As of March 1, 2014, RTOG will join with the National Surgical Adjuvant Breast and Bowel Project and the Gynecologic Oncology Group to conduct cancer research as NRG Oncology—one of four adult cancer research groups conducting multi-institutional clinical trials within the NCI’s National Clinical Trials Network. NRG Oncology seeks to improve the lives of cancer patients by conducting practice-changing multi-institutional clinical and translational research with emphases on gender-specific malignancies including gynecologic, breast, and prostate cancers and on localized or locally advanced cancers of all types.

The American College of Radiology (ACR) is a national professional organization serving more than 32,000 radiologists, radiation oncologists, interventional radiologists and medical physicists with programs focusing on the practice of radiology and the delivery of comprehensive health care services.

​OSUCCC-James Media Contact: Amanda J. Harper, OSUCCC-James Director of Media Relations,  614-685-5420 (direct), 614-293-3737 (central line) or Amanda.Harper2@osumc.edu.

RTOG Media Contact: Nancy Fredricks, ACR Clinical Research Center Director of Communications, 610-715-7707 or nancy.fredricks@acr.org



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