Promising Treatment for Glioblastoma Brain Tumors
- The late Senator John McCain bravely battled an aggressive form of brain cancer amid a glioblastoma diagnosis. He passed away from the disease in August 2018. Now, early results from a clinical trial shows promise in treating this difficult type of tumor.
- Glioblastoma (GBM) “grows and spreads very quickly,” according to the National Cancer Institute. The average survival rate is 15 months with treatment and less than six if left untreated. However, early results in an ongoing clinical trial offer a glimmer of hope for patients living with GBM.
- Early results in a phase 1 clinical trial published in The New England Journal of Medicine found three patients who saw major reductions in their GBM brain tumors, and one of them saw her tumor experience “near-complete tumor regression.”
- Researchers made such progress using a form of CAR T-cell therapy, a cancer treatment that re-engineers the immune system to target cancer. The re-engineered cells are designed to be “directly injected into the patient’s brain” by targeting a protein often found in glioblastomas called EGFR.
- Clinical trials give patients a chance to try a treatment before it’s approved by the U.S. Food and Drug Administration (FDA), and that can potentially be life-changing for patients.
Despite the great benefits that come from clinical trials, they also come with risks (like potential side effects that are not fully understood yet). People interested in participating in clinical trials must first talk with their doctor to see if they would be a good fit.
For help finding a clinical trial that’s right for you, try our easy-to use Clinical Trial Finder. - Glioblastoma symptoms include seizures, headaches, changes in speech, and difficulty balancing.
- One of the reasons glioblastomas are difficult to treat is surgery often cannot remove all of the GBM tumor cells because of the way the tumor burrows into the brain.
Former U.S. Senator and war hero John McCain died from an aggressive form of brain cancer called glioblastoma. Despite being difficult to treat, ongoing clinical trials are showing promise for this challenging brain tumor and raising hopes for patients impacted by it.
Other notable people diagnosed with glioblastoma include former U.S. Senator Ted Kennedy and President Joe Biden’s son, Beau.
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“The CAR-T platform has revolutionized how we think about treating patients with cancer, but solid tumors like glioblastoma have remained challenging to treat because not all cancer cells are exactly alike, and cells within the tumor vary. Our approach combines two forms of therapy, allowing us to treat glioblastoma in a broader, potentially more effective way,” Dr. Bryan Choi, a neurosurgeon and associate director of the Center for Brain Tumor Immunology and Immunotherapy, Cellular Immunotherapy Program at Mass General Cancer Center and Department of Neurosurgery said in a news release.
A Clinical Trial with Promising Results
The CAR T cell therapy doctors used during the clinical trial used a variant called CAR-TEAM.
CAR T-cell therapy works by re-engineering a patient’s immune cells into more efficient cancer fighters. The process starts with T-cells, white blood cells that help the immune system respond to threats in the body, such as germs and cancer cells.
After the T-cells are removed from a patient’s blood, doctors use an inactivated virus to insert new genes into them. The new genes carry instructions to create special proteins called receptors on the T-cell’s surface. The modified T-cells are multiplied and then given back to the patient.
Once the re-engineered cells are re-inserted into the body, the T-cells find and attach to a matching protein called an antigen on the surface of the cancer cells.
During the clinical trial, doctors combined CAR T cell therapy with “bispecific antibodies, known as T-cell engaging antibody molecules (TEAMS).” The combined CAR T cell therapy is called CAR-TEAM. It’s designed to be “directly injected into the patient’s brain” by targeting a protein often found in glioblastomas called EGFR.
During the clinical trial, a 74-year-old man diagnosed with a glioblastoma brain tumor and treated with a single infusion of CAR-TEAM saw his tumor “regress rapidly.”
Another patient, a 72-year-old man, was given a single infusion of CAR-TEAM cells. After two days, his tumor shrunk in size by “18.5%,” and after 69 days, his tumor shrunk by “60.7%.” The CAR-TEAM cell treatment response lasted “over six months.”
The third patient, a 57-year-old woman, was treated with a single infusion of CAR-TEAM cells, and after five days, her tumor showed “near-complete tumor regression.”
“These results are exciting, but they are also just the beginning—they tell us that we are on the right track in pursuing a therapy that can potentially change the outlook for this intractable disease. We haven’t cured patients yet, but that is our audacious goal,” Dr. Marcela Maus, director of the Cellular Immunotherapy Program at the Mass General Cancer Center, said.
As the clinical trial continues, the team of researchers hopes to find ways to prolong the CAR-TEAM cell treatment’s effectiveness, as two of the three patients experienced a relapse after some time.
More on CAR T Therapy
Dr. Siddhartha Ganguly is a Carol Cockrell Curran Distinguished Centennial Chief in Hematologic Oncology at Houston Methodist Hospital and Neal Cancer Center. He describes the process of making CAR T-cell therapy a reality, similar to the popular video game Pacman.
“CAR-T therapy aims to give “eyes” to the T-cells. We remove the T-cells from the body by a blood draw, send them to the lab, and insert an anti-cancer gene before infusing them back into the patient. This gene allows the T-cell to “see” the cancer cells…They will seek out the cancer and kill it, much like the video game Pacman,” Dr. Ganguly told SurvivorNet.
Dr. Ganguly says he’s been using this form of treatment on patients for years and emphasizes the hope it offers patients battling diseases like advanced lymphoma or myeloma. He adds that although CAR T-cell therapy, like most treatments, has its side effects.
The FDA has approved the following drugs so far:
- Abecma (idecabtagene vicleucel)
- Breyanzi (lisocabtagene maraleucel)
- Carvykti (ciltacabtagene autoleucel)
- Kymriah (tisagenlecleucel)
- Tecartus (brexucabtagene autoleucel)
- Yescarta (axicabtagene ciloleucel)
These drugs help treat blood cancers like lymphomas, some forms of leukemia, and, most recently, multiple myeloma. While these therapies offer potential benefits for patients impacted by various cancer types, the FDA is investigating the risk of T-cell malignancy in CAR T-cell therapy.
Ongoing Efforts to Improve Glioblastoma Treatment
Neuro-oncologist at Duke University Medical Center, Dr. Henry Friedman, has been researching glioblastoma, the most aggressive primary brain tumor, for years. He says he wants to offset the notion your time is limited just because you’re faced with a glioblastoma diagnosis.
He and his colleagues at Duke have been researching a new therapy that combines a modified poliovirus and immunotherapy. The modified poliovirus is used to treat glioblastoma brain tumors. Immunotherapy is a cancer treatment that uses the body’s immune system to combat cancer cells from within.
Dr. Friedman shared the therapy works by injecting the modified poliovirus directly into the tumor through a catheter. It lyses the tumor. Tumor lysis occurs when cancer cells fall apart and flood the bloodstream faster than the body can rid itself of them due to cancer treatment such as chemotherapy.
“[The process] causes the tumor cells to basically break up,” Dr. Friedman explained.
Although research paused due to resource allocation, Dr. Friedman says a new trial will differ from how his team treated glioblastoma tumors.
“Now we’re injecting poliovirus into the wall of the crater of the tumor because that’s where most tumor cells reside. We’re also injecting it into the lymph nodes on the same side the tumor is located in the body,” Dr. Friedman explained of the modified approach.
“With repetitive dosing of poliovirus immunotherapy, hopefully, we can boost the 5-year survival rate beyond 20 percent,” Dr. Friedman said.
Most of all, he hopes the ongoing research at Duke Cancer Institute offers patients more hope.
“So many people are never offered any hope when it comes to glioblastoma, and they’re told nothing can be done…nothing will be easy, but that [defeatist mentality] is garbage,” Dr. Friedman said.
Dr. Friedman said checkpoint inhibitors are not very effective in treating glioblastoma. Checkpoint inhibitors are a class of immunotherapy drugs specifically targeting proteins found on immune or cancer cells to prevent their binding.
Understanding Glioblastoma Tumors
Glioblastoma is considered a central nervous system (CNS) tumor. Burrell’s tumor is considered grade 4, which means her brain tumor “grows and spreads very quickly,” according to the National Cancer Institute.
According to the National Cancer Institute, the average survival rate is 15 months with treatment and less than six if left untreated. While there is a five-year survival rate of averaging 6 percent, those individuals will never be cancer-free and must continue receiving radiation and chemotherapy for the rest of their lives. Again, Dr. Friedman aims to boost the survival rate beyond 20% with his poliovirus and immunotherapy still undergoing research.
Glioblastomas are tricky to treat and manage because their cells are heterogeneous, meaning that each one must be individually targeted to slow tumor growth. Surgery cannot remove all the cancer because the tumor burrows into the brain, so the tumor starts to grow again immediately after surgery.
Glioblastoma risk factors can include:
- Prior radiation exposure
- Gender: men are more likely to get glioblastoma than women
- Age: people 50 years or older
- Certain genetic syndromes, including neurofibromatosis, tuberous sclerosis, von Hippel-Lindau disease
Symptoms for glioblastoma can vary depending on the area of the brain where the tumor begins and spreads and its growth rate, according to MD Anderson Cancer Center. But common symptoms of glioblastoma can include:
- Headaches
- Seizures
- Changes in mental function, mood, or personality
- Changes in speech
- Sensory changes in hearing, smell, and sight
- Loss of balance
- Changes in your pulse and breathing rate
Current Options to Treat Glioblastoma
Although glioblastomas are difficult to treat, the Food and Drug Administration’s (FDA) approval of the drug temozolomide (Temodar) was a massive breakthrough in helping patients with this aggressive disease.
Temozolomide is a chemotherapy drug patients can take after surgery and radiation therapy.
Dr. Daniel Wahl, professor of radiation and oncology at the University of Michigan, explains Temozolomide is an oral drug that works by “slowing down tumor growth.”
“Patients with GBM have effective treatment options; there are four of them: surgery, radiation, chemotherapy, and tumor targeting fields. These are electric fields that we can use to treat these cancers,” Dr. Wahl said.
Other FDA-approved drugs for treating glioblastoma include lomustine (Gleostine), intravenous carmustine (Bicnu), carmustine wafer implants, and Avastin (bevacizumab).
Avastin is a targeted drug therapy that blocks glioblastoma cells from requesting new blood vessels that feed and allow the tumor to grow.
“Outcomes for these patients are still suboptimal. What I tell my patients is that we have these effective treatments, but what they do is they delay the time to when this tumor comes back. Only in exceptional circumstances would we ever talk about getting rid of one of these cancers a few,” Dr. Wahl said.
WATCH: Using electric sources to improve glioblastoma treatment.
Fortunately, research is ongoing to improve the prognosis for people battling glioblastoma. One area of promise is tumor-treating fields, which can help extend patients’ lives by two years on average, giving them hope.
Optune, the brand name for the tumor-treating field delivery device, was launched in 2011 and approved by the FDA in 2015. It is a wearable and portable device for glioblastoma treatment for adult patients aged 22 years or older.
“There’s been a very exciting development of tumor treating fields, which are electrical fields that have been applied to the brain,” Dr. Suriya Jeyapalan, a neurologist at Tufts Medical Center, previously told Survivor Net.
TTFields use low-intensity electric fields to disrupt the cell division process, making it harder for cancerous cells to multiply.
Despite Optune’s hope, not all cancer experts agree with its approach, including Dr. Friedman.
“Although the National Comprehensive Cancer Network (NCCN) recognizes Optune within its guidelines as a therapy for glioblastoma, many people don’t believe it adds value. At Duke, for example, we don’t consider it a mainstay of therapy,” Dr. Friedman said.
Questions for Your Doctor
If you have been diagnosed with glioblastoma, here are some questions you may consider asking your doctor:
- What stage is my brain cancer?
- What are the treatment options for my brain cancer?
- What are the risks and benefits of the recommended treatment?
- What are the side effects of the recommended treatment?
- How long will it take to recover from treatment, and will I be able to return to work and normal activities?
- What’s the likelihood that insurance will cover the recommended treatment?
- Am I a good candidate for temozolomide, Optune, or clinical trials?
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