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In a recently published manuscript, Howard Colman, MD, PhD, Jon M. Huntsman Presidential Professor of Neuro-Oncology and co-leader of the Neurologic Cancers Disease Center and the Experimental Therapeutics CCSG program at Huntsman Cancer Institute, identified a potential breakthrough in glioblastoma treatment.
Glioblastoma, or GBM, is an aggressive type of brain cancer. According to Colman, this is the most common type of cancerous brain tumor in adults. Standard treatments include radiation and chemotherapy. Unfortunately, typical GBM tumors are often resistant to these treatments and only respond for a matter of months. Due to the aggressive nature of this cancer, tumors often recur and spread.
“Typically, when patients have a recurrence of GBM, and you put them on a new drug, the tumor only stays in check for one to two months,” says Colman. “We are constantly looking for better treatments and doing clinical trials to try and identify new ways to help our patients with GBM.”
Currently in phase 2, this clinical trial tested the use of two experimental agents for glioblastoma – a novel viral therapy and a drug that activates the immune system. This specific immunotherapy, called a checkpoint inhibitor, blocks proteins made by cancer cells that help them hide from a patient’s own immune system. While immunotherapy uses a patient's immune system to help fight cancer growth and has been successful in other cancer types, these drugs generally have not been effective when used alone in GBM treatment. This is where the viral therapy comes in.
Using a modified virus normally responsible for minor infections and the common cold, researchers created a treatment that specifically attacks tumor cells, while leaving normal cells intact.
Clinicians inject the virus directly into the patient’s tumor, and the patient receives the checkpoint inhibitor called pembrolizumab through an IV on a recurring schedule.
“The idea here is that the virus kills some of the tumor cells and the dying tumor cells then help turn on the patient’s immune system,” says Colman. “We then give the patient a checkpoint inhibitor, which further activates the immune system’s response against the tumor. This is potentially a significant advance, as GBM does not typically respond to immunotherapy.”
During the initial phase, researchers focused on finding the correct dose and assessing safety of both agents. In phase 2, they looked at the percentage of patients who saw improvement in the size of their tumor, delay in progression of tumor, and overall survival.
Around 10% of patients enrolled in this trial experienced tumor shrinkage, with two tumors demonstrating a complete response. Patients who experienced shrinkage also appeared to have delayed tumor growth and lived much longer than expected.
“While this treatment appeared to only help a subset of patients in this trial, the hope is that we’ll be able to improve survival significantly for some GBM patients, while at the same time, working to try and find other effective therapies for patients where this combination doesn’t work,” says Colman.
This is full-circle moment for Colman, who worked on the early stages of the modifying the virus during his time at MD Anderson from 2002-2010.
Huntsman Cancer Institute accrued many patients for this trial and plans to continue to work on the future development of this combination therapy for GBM, as well as many other experimental treatments currently in clinical trials.