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Could a new combo therapy improve prognosis for people with the most aggressive form of brain cancer? Image credit: Amornrat Phuchom/Getty Images.
  • Researchers investigated a novel combination treatment involving an oncolytic virus and immunotherapy for recurrent glioblastoma.
  • The treatment increased survival rates from 6–8 months to 12.5 months.
  • Further studies are needed before the treatment can be used on patients.

Glioblastoma is the most aggressive form of brain tumor in adults, and it accounts for 49.1% of all primary malignant brain tumors.

Around 14,000 cases of glioblastoma are diagnosed each year in the United States. Men are 1.6 times more likely than women to develop the condition, and Caucasians are more likely to have glioblastoma than other ethnicities.

The current standard of care for newly diagnosed patients involves surgery and chemoradiotherapy. However, the condition recurs in many of these patients after treatment.

On average, patients with glioblastoma survive for 6-8 months after their first diagnosis, and the 5-year survival rate is 6.8%.

Research into effective treatments is essential for improving outcomes and survival rates for patients with glioblastoma.

Recently, researchers investigated the safety and effectiveness of a new therapy that combines an oncolytic virus — a genetically-modified virus that targets and kills cancer cells — and intravenous immunotherapy.

The treatment eradicated tumors in certain patients and increased average survival from 6-8 months to 12.5 months.

Dr. Jay-Jiguang Zhu, a neuro-oncologist with McGovern Medical School at UTHealth Houston, not involved in the study, told Medical News Today:

“[This study] shows to the world that such a combination can be done, and it is safe. It is exciting and significant work! Also, given the current dosing and regimen, it is likely to help patients with glioblastoma. But hopefully further improvement of this regimen can provide more benefit to glioblastoma patients.”

The study was published in Nature.

Immune checkpoint inhibitors (ICIs) are a type of immunotherapy that works by blocking certain proteins that moderate immune function. In doing so, they stop the immune system from turning off before cancer cells are killed.

While ICIs have improved outcomes for a variety of cancers, results have been limited in glioblastomas as their microenvironment is immunosuppressive. Previous studies have shown that oncolytic viruses can make the tumor microenvironment more susceptible to ICIs.

Dr. Manmeet S. Ahluwalia, chief of solid tumor medical oncology, deputy director and chief scientific officer at Miami Cancer Institute, part of Baptist Health, not involved in the study, explained to MNT that “[o]ncolytic viruses are a type of virus that are designed or modified to selectively infect and destroy cancer cells while sparing healthy cells.”

”When combined with oncolytic viruses, checkpoint inhibitors can further enhance the activation and proliferation of tumor-specific T cells, resulting in improved tumor control,” he noted.

For the study, researchers conducted a phase 1/2 clinical trial to treat recurrent glioblastoma via an oncolytic virus and pembrolizumab — an ICI used to treat conditions including lung cancer, head and neck cancer, and melanoma.

To do so, they enrolled 49 patients with glioblastoma at an average age of 53 years old. All patients had previously received radiotherapy and temozolomide- a drug that works by stopping the growth of cancer cells in the body.

In the trial, patients were treated with one dose of the oncolytic virus, and pembrolizumab 7 days later for an average of 153 days. Three patients completed a full two-year course of pembrolizumab therapy.

Ultimately, only 10.4% of patients responded to the drug combination. However, patients survived for an average of 12.5 months — a significant increase from the 6–8 months with existing therapies.

Meanwhile, 56.2% of patients reported stable disease or better, and three patients completed treatments with durable responses and remained alive 45, 48, and 60 months later.

Dr. Naveed Wagle, a neuro-oncologist at Pacific Neuroscience Institute in Santa Monica, CA, and associate professor of translational neurosciences at Saint John’s Cancer Institute in Santa Monica, CA, not involved in the study, told MNT:

“The brain is thought to be a protective environment and keeps most immune processes from functioning as they would in the body. […] In cancer care, it unfortunately also means that many immunotherapies are not as effective in treating cancer in the brain and certainly in treating gliomas.”

“In this study, the researchers used an oncolytic virus that selectively replicates in the cancerous cells. This allows the immune system to be able to target these cells. It also potentially allows immunotherapy such as checkpoint inhibitors to work on these cells,” he added.

When asked about what the findings may mean for treating glioblastoma, Dr. Wagle noted that the study is still early stage. While the doses show good safety results, he noted that the study does not show that the treatment is effective for treating gliomas.

“The results are promising but not conclusive of efficacy. The study is not big enough to evaluate the efficacy of this type of therapy,” he noted.

“The main positive implication of this study is the oncolytic virus can change the immune environment in the cancer/glioma environment. This could potentially allow immunotherapy to be more effective in combating the cancers of the brain. Viral therapy can be a potential treatment therapy but also a means to allow other therapies to work better in the brain,” he concluded.