From Karyn M. Dyehouse, MD, Neuro-oncologist with OHC

November 28, 2018

Glioblastoma (GBM) is one of the most aggressive forms of brain cancer in adults. Most recently, the country lost Arizona Senator John McCain to this incurable type of cancer. Although there is still no cure, there have been some advances in the treatment of GBM.

One potential advancement is immunotherapy, a treatment that works by triggering the immune system to attack tumors. It has proven to be effective against a growing number of cancers and the hope is that it can eventually work against glioblastoma.

Several immunotherapy treatments looked highly promising in early phase of clinical trials of patients with glioblastoma. However, they haven’t yet worked out in phase 3 clinical trials.

Many of us were excited to learn that some of the treatments made it to phase 3 trials. That’s encouraging news.

Glioblastoma has always been one of the most difficult cancers to treat. One reason is the physiology of the tumor. It doesn’t have a defined area of normal tissue surrounding the tumor, so it’s difficult to remove most of it through surgery.

Another reason is the ‘blood-brain barrier,’ which protects the brain from things like viruses and toxins – and in some cases, chemotherapy drugs.

Another challenge for researchers is that the immune system works very differently in the brain than other organs in the body. The brain appears to have a different mix of immune cells and, as a result, it doesn’t readily generate an immune response against tumors the way they do in other organs. Many of the immune cells in and around glioblastoma tumors tend to be severely impaired.

Steroids are often used to control potentially dangerous brain swelling and manage treatment-related side effects in patients with glioblastoma. Research has also shown that steroids can interfere with the immune response. So, in the first-ever phase 3 trial of an immune checkpoint inhibitor in glioblastoma, called Checkmate 143, the drug nivolumab (Opdivo) failed to increase how long patients with advanced glioblastoma lived. That’s because approximately 40 percent of patients in the trial who received nivolumab were also taking steroids, which means the drug may not have been able to work effectively.

Although Checkmate 143 was unsuccessful with glioblastoma, checkpoint inhibitor therapy is tested most widely in glioblastoma. The therapy targets immune checkpoints, the key regulators of the immune system that stimulate or inhibit its actions. Tumors can use checkpoints to protect themselves from the immune system. Checkpoint therapy can block inhibitory checkpoints, allowing the immune system to work against the tumor.

Multiple checkpoint inhibitors have been approved by the Food and Drug Administration (FDA) for a growing list of cancer types, and a number of these drugs are being tested in early- and late-phase clinical trials in patients with glioblastoma. They are also being tested in combination with other therapies, including other forms of immunotherapy. And there’s some evidence from animal studies that these immunotherapy combinations may be what’s needed to make checkpoint inhibitors work in glioblastoma.

Another potential treatment for patients with recurrent GBM is bevacizumab (Avastin), a “tumor-starving” (anti-angiogenic) therapy. Avastin is designed to prevent the growth of new blood vessels including those that feed tumors and allow them to grow. It’s currently being studied in clinical trials, and is often used in combination with checkpoint inhibitors. Its continued approval is based upon the results of studies aimed at demonstrating the effectiveness of the drug.

In an article in the July 2018 issue of CURE, a woman in New York who was diagnosed with glioblastoma asked her doctor about the clinical trial studying Avastin. Her treatment was administered directly to her tumor, as opposed to intravenously. She responded so well to this one-time treatment that she felt as if a fog had cleared when she woke up. “I went in to the procedure pretty confused,” she reported. “But when I woke up, I knew where I was. I knew that my husband was waiting for me in the ICU step down unit. I knew what I had just been through. I asked the nurse, ‘This is crazy, but could this have already worked?’”

This is remarkable but we’re very careful when discussing the potential of any treatment that is still in the study phase. Patients can have atypical responses or complications down the road. There is definitely growing optimism, but that’s cautious optimism. There is much work to be done before any treatment becomes standard of care.

Thirty percent of patients with glioblastoma will survive two years, and of those that make it to two years, half will make it to three years. And then there are the five-year survivors. A 2009 study found that as many as 10 percent might make it this far. Some live even longer.

The key message is that with each day and each step, we’re extending the survival period. We don’t have a cure yet, but researchers are making progress. We’re getting a better understanding of how cancer develops and grows – and how we can stop it.

For more information about glioblastoma and treatments, or to learn how OHC is bringing together the latest treatments and support services for their patients, contact OHC at 1-888-649-4800 or visit Dr. Dyehouse serves as the leading neuro-oncologist at the Brain Tumor Center at The Jewish Hospital – Mercy Health, which provides patients with access to exceptional surgical services and innovative technology for the treatment of brain tumors.

Sources: National Cancer Institute, Cancer Research Foundation, National Brain Tumor Society

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