Clinical trial of combination therapy shows great promise for glioblastoma patients

A new international study published in natural medicine Presented as a modern abstract at the Annual Meeting of the American Association of Neurological Surgeons (AANS), the paper shows great promise for patients with glioblastoma.

Doctors. Farshad Nassiri and Gerare Zadeh, neurosurgeons at the University Health Network (UHN) in Toronto, investigate the safety and efficacy of a new treatment that combines injections of oncolytic virus (oncolytic virus). announced the results of a Phase 1/2 clinical trial. Intravenous immunotherapy targets and kills cancer cells directly at the tumor.

The authors found that this novel combination therapy could eradicate tumors and prolong survival in selected patients.

The authors’ research study also uncovered novel genetic features within tumor samples that may predict which glioblastoma patients are most likely to respond to treatment.

Initial clinical trial results are promising. We are cautiously optimistic about the long-term clinical benefits for patients. ”

Dr. Gerare Zadeh, Co-Director, Crenville Brain Institute, Principal Investigator, Princess Margaret Cancer Center

Glioblastoma is a primary brain tumor notoriously difficult to treat. Despite aggressive treatment, which usually includes surgical removal of the tumor and multiple chemotherapy drugs, the cancer often recurs, at which point treatment options are limited.

Immune checkpoint inhibitors are effective therapies for various cancers, but have been less successful in treating recurrent glioblastoma.This new treatment includes a combination of oncolytic viruses and Immune checkpoint blockade using anti-PD-1 antibodies as targeted immunotherapy.

First, the team used stereotaxic techniques to pinpoint the location of the tumor and delivered the virus by injecting it through a small hole and a purpose-built catheter. After that, the patient received anti-PD-1 antibodies intravenously every 3 weeks from her 1 week after surgery.

“These drugs work by interfering with the cancer’s ability to evade the body’s natural immune response, so they rarely work when the tumor is immunologically inactive, as is the case with glioblastoma. It doesn’t work,” explains Dr. Zadeh.

“Oncolytic viruses overcome this limitation by creating a more favorable tumor microenvironment, which helps promote anti-tumor immune responses.”

The combination of oncolytic viruses and immune checkpoint blockade provides a ‘double attack’ on tumors. The virus not only directly causes cancer cell death, but also stimulates local immune activity, causing inflammation and making cancer cells more vulnerable to targeted immunotherapy.

Dr. Zadeh and colleagues evaluated an innovative treatment in 49 relapsed patients from 15 hospitals across North America.

UHN is Canada’s largest research and teaching hospital and the only Canadian institution involved in this study, and treated the majority of patients enrolled in this trial.

Result is, natural medicine, indicating that this combination therapy is safe, well-tolerated, and prolongs patient survival. The treatment had no major unanticipated side effects, and his median survival was 12.5 months, considerably longer than the 6-8 months typically seen with existing treatments.

“We are very encouraged by these results,” says Dr. Farshad Nasiri, lead author of the study and senior neurosurgical resident at the University of Toronto. “More than half of patients achieve clinical benefit, stable disease or better, significant response, including tumor shrinkage, and some even complete resolution. Three patients are alive at 45, 48 and 60 months after the start of the trial.”

“Patients in the trial did not undergo tumor resection at the time of recurrence, only virus injections. The findings of this study are particularly significant as this is a new treatment for glioblastoma. It’s really remarkable to see the reaction,” he said. Dr. Zadeh.

“We believe that the key to our success was delivering the virus directly to the tumor prior to using systemic immunotherapy. Our results show that this is a safe and effective approach. It clearly shows that there is potential,” added Dr. Nassiri.

The research team also performed experiments to determine the mutations, gene expression and immune characteristics of each patient’s tumor. They discovered important immune signatures that may ultimately help clinicians predict treatment response and understand the mechanisms of glioblastoma resistance.

“In general, drugs used to treat cancer do not work for all patients, but we believe there is a subpopulation of glioblastoma patients who respond well to this treatment,” Zadeh said. says Dr. “We believe this translational work, combining basic science and clinical trials, will be the key to advancing personalized treatment for glioblastoma.”

This was one of the few clinical trials in the last decade with positive results for glioblastoma, and it was truly a team effort.

“This trial would not have been possible without our amazing operating room team, including Dr. Warren Mason and her team at Princess Margaret Cancer Center, our research safety team, our researchers, and our brave patients and their families. I would also like to thank the Wilkins “family for funding the completion of a clinical trial that will advance their patient’s care,” Dr. Zadeh said.

The group’s next step is to test the efficacy of the combination against other treatments in randomized clinical trials.

“We are encouraged by these results, but there is still much work ahead of us,” says Dr. Nassiri. “Our goal, as always, is to help patients. That’s what motivates us to continue this research.”