A potential advancement in the treatment of glioblastoma was noted by Howard Colman, MD, PhD, the 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, in a recently published manuscript.
Glioblastoma, or GBM, is a particularly severe form of brain cancer. This is the most prevalent form of a malignant brain tumor in adults, according to Colman. Radiation and chemotherapy are common therapies.
Unfortunately, standard GBM tumors are frequently resistant to these treatments and only react for a few months. Tumors frequently return and spread due to the aggressive nature of this malignancy.
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. We are constantly looking for better treatments and doing clinical trials to try and identify new ways to help our patients with GBM.”
Howard Colman, MD, PhD, Jon M. Huntsman Presidential Professor, Department of Neurosurgery, University of Utah
This research trial, which is currently in phase 2, examined the efficacy of two new viral treatments and an immune system stimulant as possible therapies for glioblastoma. A checkpoint inhibitor is a particular type of immunotherapy that prevents cancer cells from producing the proteins that enable them to evade the body’s immune system.
otherapy, which employs the patient's immune system to fight cancer growth, has been successful in treating other cancer types, it has not often been successful when used alone in the treatment of GBM. The viral treatment is used in this situation.
Researchers developed a drug that specifically targets tumor cells while sparing healthy cells, using a modified virus that is typically responsible for mild infections including the common cold.
The checkpoint inhibitor called pembrolizumab is administered to the patient via an IV on a regular basis, and the virus is directly injected by medical professionals into the patient’s tumor.
Colman added, “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. 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.”
Researchers initially concentrated on determining the proper dose and evaluating the safety of both drugs. In phase 2, they examined the proportion of patients whose tumor size improved, whose tumor growth was slowed down, and whose overall survival increased.
Around 10% of patients in this experiment saw tumor reduction, with two tumors showing a complete response. Patients who underwent tumor-shrinking appeared to have postponed tumor growth and lived considerably longer than expected.
Colman added, “While this treatment appeared to only help a subset of patients in this trial, the hope is that we will 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.”
This is a full-circle experience for Colman, who worked on the early stages of virus modification at MD Anderson from 2002 to 2010.
The Huntsman Cancer Institute enrolled a large number of patients for this trial and intends to continue working on the future development of this combination therapy for GBM, as well as a number of other investigational drugs now in clinical studies.