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Fighting the Deadliest Brain Cancer, Glioblastoma

February 28, 2017

Researchers at Yale Medicine are working to harness the immune system to battle glioblastoma.

Tremendous progress has been made in extending the life expectancy for patients suffering from glioblastoma, the deadliest of brain cancers. Forty years ago, patient with this cancer diagnosis were given four months to live. Now the median life expectancy is more than 14 months.

For years, physicians sought to attack glioblastoma from the outside, using chemotherapy, drugs, or radiation. But one of the new frontiers in glioblastoma treatment turns this inside out, using immunotherapy to fight the disease.

Right now there is a good scientific rationale for using these treatments for patients with brain tumors, because the targets are truly there.

Joachim Baehring, MD

As a glioblastoma takes hold in the brain, the body’s immune system tries to seek out and destroy it, just as it would with bacteria, fungi, or a virus. But the rapidly growing cancer retaliates by putting the immune system in lock-down mode. Scientists believe that stimulating the immune system could free it to fight the cancer. Now, Yale Medicine doctors are running several high-profile, national clinical trials to learn how to unlock the immune response.

A 'big breakthrough'

“Immunotherapy is one of the big breakthroughs—for a long time thought of as the holy grail,” says Kevin Patrick Becker, MD, a Yale Medicine neurologist who has been investigating immunotherapy alongside Joachim Baehring, MD, clinical program leader of the Brain Tumor Program at Smilow Cancer Hospital.

Dr. Baehring expects preliminary results to be announced in 2017 for a key multi-site clinical trial of nivolomub—one of several drugs known as PD-1/PD-L1 inhibitors, which help a patient’s immune system recognize and attack cancer. (Nivolomub is manufactured by Bristol-Myers Squibb under the trade name Opdivo.) The drug has shown dramatic success in treating other cancers. Earlier this year, it was approved by the Food and Drug Administration for metastatic lung cancer, showing a 41 percent increase in overall survival over the existing standard of care. Roy Herbst, MD, chief of medical oncology at the Yale Cancer Center, has called those results “miraculous.”

... but a cautious approach

But Dr. Baehring takes a cautious approach when it comes to new treatments for glioblastoma. He remembers when the drug Avastin came out. It was supposed to slow the growth of new blood vessels and starve tumors. “When Avastin was introduced, we thought, ‘This is it. This is going to help a substantial number of patients with this disease,’” he says. “Avastin has its place now in treating glioblastoma, but it did not turn out to be as promising as the initial data implied."

Nivolomub does show promise in that it has been used to treat as many as 11 other cancers, Dr. Baehring says, noting that many of these have similar "markers" to glioblastoma. (This refers to a substance that can be detected in higher-than-normal amounts in the blood, urine, or body tissues of some patients with glioblastoma.) “Right now there is a good scientific rationale for using these treatments for patients with brain tumors, because the targets are truly there,” he says.

Both doctors say they hope they can someday use immunotherapy and other new approaches to finally start to control what has been a terminal illness.