Immunotherapy drug can be effective in treating patients with recurrent brain tumors

The research conducted by UCLA could be step to a new therapy for brain cancer difficult to treat

A study conducted by UCLA suggests that for people with recurrent glioblastoma, administering an immunotherapy drug before surgery is more effective than the subsequent use of the drug.

In recent years, it has been shown that immunotherapy drugs, which harness the body's immune system to destroy cancer cells, are useful in treating people with advanced or metastatic cancer. But the drugs still have no benefit in helping people with glioblastoma, an aggressive and deadly form of brain cancer. On average, most people with recurrent glioblastoma live only six to nine months.

The study, published in Nature Medicine, was led by Robert Prins, Professor of Molecular and Medical Pharmacology at UCLA's David Geffen School of Medicine, and Dr. Timothy Cloughesy, Professor of Neuro-Oncology at the Geffen School of Medicine. Both are scientists at the UCLA Jonsson Cancer Center. It shows for the first time that pembrolizumab, an immune checkpoint inhibitor drug marketed under the brand name Keytruda, may be effective in treating people with recurrent glioblastoma.

In the study, people treated with the drug before surgery lived nearly twice as long after surgery as the average life expectancy of people with the disease.

Pembrolizumab is an antibody that blocks a control point protein called PD-1 that prevents T cells from attacking cancer cells. Cancer cells often use PD-1 to keep the T cells at bay. But inhibiting the commitment of the protein with a checkpoint inhibitor drug like pembrolizumab allows the immune system to better fight against cancer.

"The results are very encouraging," said Prins, lead author of the study. "This is the first clue that immunotherapy can have a clinical benefit for patients with malignant brain tumors – and help prevent future recurrences."

The trial, which was conducted in seven US medical centers, evaluated 35 people with recurrent glioblastoma that could be surgically resected – meaning that tumors could be removed by surgery. Of these, 16 received pembrolizumab prior to surgery and 19 received the drug thereafter.

Those who received the drug before the surgery survived on average 417 days, those who received the drug after the surgery lived on average 228 days.

"By administering immunotherapy before surgery, we activated tumor T cells, which previously had impaired function, which is essentially what has helped to prolong people's lives," said Cloughesy.

In a person with cancer, if antigen-specific T cells are present and impaired by the tumor and the surrounding microenvironment, they may be awakened by the drug before surgery. On the other hand, after the surgery, the drug does not stimulate the T cells of the patients because they are eliminated with the tumor.

The results could be significant, as there have been few major advances in the treatment of glioblastoma in the last two decades and this could be a step in the development of new biomarkers of disease.

"These data could lead us to better understand the mechanisms by which some patients generate significant immune responses to this therapy, but not the others," said Prins, who is also a member of the research group at the Center for Research on Cancer. Cancer Infection from the Parker Institute at UCLA. "It can also help us determine which drug combination might be the most effective for each patient."

The team is currently testing immunotherapy in combination with vaccines and other control point inhibitors.

"This is not a very big study, and our data needs to be replicated, but we have a foot in the door," Cloughesy said. "We have found a way to use these checkpoint inhibitors in glioblastoma, which we previously thought ineffective.We now have a rational and logical way to develop immunotherapies and a clinical development process to do it. "