Bevacizumab and Temozolomide in First Recurrence of Glioma Without 1p/19q Codeletion

Excerpt:

“In a phase II trial funded by the European Organisation for Research and Treatment of Cancer and reported in The Lancet Oncology, van den Bent et al found no evidence of a survival benefit with the addition of bevacizumab (Avastin) to temozolomide in patients with a first recurrence of World Health Organization grade II or III glioma without the 1p/19q codeletion.

“In the open-label trial, conducted at 32 European centers, 155 patients were randomized between February 2011 and July 2015 to receive either temozolomide at 150 to 200 mg/m² on days 1 to 5 every 4 weeks for a maximum of 12 cycles (n = 77) or the same temozolomide regimen plus bevacizumab at 10 mg/kg every 2 weeks until disease progression (n = 78). Previous chemotherapy must have been stopped at least 6 months before enrollment, and radiotherapy, at least 3 months before enrollment. Overall, 44% of patients in the combination group and 47% in the temozolomide group had grade III disease.”

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Durable Responses Observed With Novel Oncolytic Therapy in Recurrent Glioma

Excerpt:

“In a pilot study of recurrent glioma, 26% of patients treated with the optimal dose of vocimagene amiretroprepvec (aka Toca 511), a novel oncolytic virus therapy, achieved durable, long-term responses and remained alive 3 or more years later. This outcome far exceeded ‘historical benchmarks’ for this poor-prognosis population, according to lead researcher Bob S. Carter, MD, PhD, the William and Elizabeth Sweet Professor and Chief of Neurosurgery at Massachusetts General Hospital, Boston.”

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Monoclonal Antibody Treatment in Newly Diagnosed Pediatric High-Grade Glioma

Excerpt:

“In a phase II study reported in the Journal of Clinical Oncology, Grill et al found that the addition of bevacizumab (Avastin) to radiotherapy plus temozolomide (RT + TMZ) did not improve event-free survival in pediatric patients with newly diagnosed high-grade glioma.

“In the international open-label study, 121 patients aged 3 to 18 years with localized nonbrainstem disease from 51 sites in 14 countries were randomized between October 2011 and February 2015 to receive RT + TMZ with (n = 62) or without (n = 59) bevacizumab 10 mg/kg every 2 weeks. RT + TMZ consisted of RT at 1.8 Gy 5 days per week and TMZ at 75 mg/m2 per day for 6 weeks followed by a 4 weeks off, then up to twelve 28-day cycles at 150 mg/m2 per day on days 1 to 5 in cycle 1 and 200 mg/m2 per day on days 1 to 5 in cycles 2 to 12. The primary endpoint was event-free survival on blinded central radiology review. Results are reported as of 12 months after the enrollment of the last patient.”

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DNX-2401 Demonstrates “Dramatic” Survival Benefit in Glioma

Excerpt:

“Treatment with the investigational agent DNX-2401 resulted in 20% of a cohort of patients with recurrent malignant glioma surviving more than 3 years from the time of treatment, according to phase I data published in the Journal of Clinical Oncology.

“In the dose-escalation study, patients were enrolled into the treatment-only group A (n = 25) or the treat-resect-treat group B (n = 12). Group A underwent stereotactic biopsy to document recurrence, followed by a single intratumoral injection of DNX-2401 at the assigned dose through the biopsy needle into the contrast-enhancing tumor mass. In group B, stereotactic biopsy and intratumoral injection of DNX-2401 through an implanted catheter was followed 2 weeks later by craniotomy with en bloc tumor resection, and then administration of a second DNX-2401 dose into several locations in the wall of the resection cavity.”

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One-Two Punch for Brain Tumors? New Clinical Trial Opens

Editor’s note: Researchers have launched a new clinical trial—a research study with volunteer patients—to test a new treatment for brain tumors. In the treatment, a patient first undergoes tumor-removal surgery. Then, a harmless virus delivers two new genes to the brain to kill any remaining cancer cells. One of the genes kills tumor cells directly and the other boosts the patient’s own immune system to attack tumor cells. Patients in the trial will also receive standard chemotherapy and radiation. Two patients are already enrolled. The trial is enrolling patients with grade 3 or 4 malignant primary glioma, such as glioblastoma multiforme.

“University of Michigan Health System doctors have started testing a unique new approach to fighting brain tumors — one that delivers a one-two punch designed to knock out the most dangerous brain cancer.

“The experimental approach, based on U-M research, delivers two different genes directly into the brains of patients following the operation to remove the bulk of their tumors.

“The idea: trigger immune activity within the brain itself to kill remaining tumor cells — the ones neurosurgeons can’t take out, which make this type of tumor so dangerous.

“It’s the first time this gene therapy approach is being tried in humans, after more than a decade of research in experimental models.”


Planned Clinical Phase I Trial to Examine the Safety of Vaccine Against Gliomas Based on Mutant IDH1 in Human Patients

“Astrocytomas and oligodendrogliomas are subtypes of a brain cancer called ‘glioma’. These incurable brain tumors arise from glial cells, a type of support cell found in the central nervous system. ‘Low-grade gliomas’, which grow comparatively slowly, spread in a diffuse manner across the brain and are very difficult to completely eliminate through surgery. In many cases, the effectiveness of treatments with chemotherapy and radiotherapy is very limited. Gliomas can develop into extremely aggressive glioblastomas.

“Low-grade gliomas have a particular feature in common: more than 70% of the cases exhibit the same gene mutation in tumor cells. An identical ‘typo’ in the DNA causes the exchange of a single, specific protein building block (amino acid) in an enzyme called isocitrate dehydrogenase 1 (IDH1). As a result, most cancer cells do not follow the original building plan for the protein; at the 132nd position in the molecule’s sequence, they insert the amino acid histidine instead of arginine…

” ‘…we might be able to use a vaccine to alert the patient’s immune system to mutant IDH1, fighting the tumor without damaging healthy cells,’ [Prof. Dr. Michael Platten at the German Consortium for Translational Cancer Research] explains.

“In collaboration with a team of physicians and scientists from Heidelberg University Hospital, DKFZ and the Universities of Mainz, Tübingen and Hamburg, Platten and his co-workers have now made the first successful step toward a vaccine that specifically targets the mutation in the tumor.

“In a clinical trial scheduled to start early next year, with the support of the German Consortium for Translational Cancer Research (DKTK), they plan to examine the safety of the vaccine against gliomas based on mutant IDH1 in human patients, for the first time.”

Editor’s note: Early next year, oncologists will begin testing a newly developed cancer vaccine in a clinical trial with volunteer patients, in the hopes that it will help treat low-grade gliomas. Cancer vaccines are a type of immunotherapy treatment; they boost a patient’s own immune system to fight cancer. The new vaccine takes advantage of a dysfunctional protein that is found in 70% of low-grade gliomas. The protein is called IDH1, and the vaccine is designed to alert the patient’s immune system to attack cells with mutant IDH1, potentially shrinking the brain tumor. So far, the vaccine has only been tested in mice, but the results were promising.