Glioblastoma — the aggressive brain cancer that killed Sen. John McCain, Sen. Ted Kennedy and Beau Biden, son of Vice President Joe Biden — is among the deadliest of cancers, with a three-year survival rate of just 10 percent. But, in a glimmer of hope, a study published Monday found that a drug designed to unleash the immune system helped some patients live longer.
The small, multisite trial led by researchers at the University of California at Los Angeles involved patients who had a recurrence of glioblastoma, the most common central nervous system cancer. It found that patients who received a drug called a checkpoint inhibitor before surgery lived for 417 days. Those who got the treatment after surgery survived 228 days, the current life expectancy for recurrent glioblastoma.
The study marked the first time this kind of immune-system treatment showed any benefit in glioblastoma patients, the researchers said.
Michael Lim, a neurosurgeon at Johns Hopkins who was not involved in the study, called the results “very interesting." He said it was one of several efforts “to disrupt the tumor a little bit" to give immunotherapy a chance to rally the immune system to attack the cancer. “I call it kindling,” he said.
Glioblastoma powerfully suppresses the immune system, both at the site of the cancer and throughout the body, which has made it difficult to find effective treatments, he said. He added that such tumors are complex and differ widely in their behavior and characteristics.
UCLA immunologist Robert Prins, senior author of the study published in Nature Medicine, said the results are “very encouraging” and will help researchers design better treatments using combinations such as checkpoint inhibitors and personalized cancer vaccines, another area attracting great interest.
But Prins, a member of the Parker Institute for Cancer Immunotherapy at UCLA, also was cautious. “We have not cured glioblastoma,” he said, adding that the trial was an early-phase study with fewer than three dozen patients.
The drug used in the trial is called pembrolizumab, and is marketed by Merck as Keytruda. The therapy was part of a successful treatment administered to former president Jimmy Carter in 2015 for advanced melanoma. Keytruda also has been approved by the Food and Drug Administration for several other malignancies, including those of the lung, bladder, and head and neck.
These checkpoint inhibitors work by blocking a protein known as PD-1. That protein prevents T-cells from seeing and attacking the cancer, so once the protein is disabled, the immune system can better go after the tumor. While the treatments are extremely effective in some patients, especially those with advanced melanoma, they help a minority of patients.
Last year, the Nobel Prize in medicine was awarded to immunologists James Allison of M.D. Anderson Cancer Center and Tasuku Honjo for discoveries leading to the development of checkpoint inhibitors for cancer.
How the drug works in glioblastoma has not been totally established, the UCLA researchers said. Like Lim, they speculated that giving the drug before surgery prompted T-cells within the tumor, which had been impaired, to attack the cancer and extend lives. The drug didn’t spur such anti-cancer activity after the surgery because those T-cells were removed along with the tumor.
Prins said that it was something of a surprise finding that the drug helped patients. The researchers gave the drug to patients preoperatively to see how the medicine affected the tumor’s “micro-environment,” not because they expected to see a clinical benefit, he said.
Hideho Okada, a neurosurgeon at the University of California at San Francisco, called the results “very important and very promising” but said they would need to be validated in much larger trials.