Keytruda May Be Effective in Helping Treat Brain Cancer

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Researchers say patients with glioblastoma who were given the immunotherapy drug before surgery lived longer.

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Experts say drugs such as Keytruda help awaken dormant T cells to fight brain tumors. Getty Images

Glioblastoma is among the most deadly forms of cancer. With treatment, the median survival time for people diagnosed with this type of brain cancer is 15 to 16 months.

But a new study shows that an immunotherapy drug could extend the life of glioblastoma patients if administered prior to surgery to remove tumors.

Researchers suspect that this is because the treatments awaken dormant T cells present in the tumor, which then can help fight the cancer wherever it appears in the brain. If the tumor is removed first, those cells are lost.

“By administering the immunotherapy before surgery, we activated the T cells within the tumor that were previously functionally impaired, which is essentially what helped extend people’s lives,” said Dr. Timothy F. Cloughesy, director of the neuro-oncology program at the University of California Los Angeles (UCLA) and a co-lead author the study. “We have found a way to use these checkpoint inhibitors in glioblastoma that we previously thought were ineffective.”

The study found that patients treated with the immunotherapy drug pembrolizumab survived for an average of 417 days while those who received the drug after surgery lived just 228 days.

That’s more than twice the life expectancy for many glioblastoma patients who die within six months of diagnosis.

“We’re obviously not curing the disease, but we at least have a foot in the door,” Robert Prins, PhD, a professor of molecular and medical pharmacology at UCLA and a co-lead author of the study, told Healthline. “Immunotherapy is a living drug. Activating cells that kill cancer cells — that’s what the immune system is designed to do.”

Pembrolizumab, marketed as Keytruda, is an antibody that blocks a “checkpoint protein” called PD-1 from inhibiting the action of the body’s cancer-fighting T-1 cells.

Glioblastomas and other cancerous tumors often use PD-1 to protect themselves from attack by the immune system.

Immunotherapy has proven to be effective in treating cancer in other parts of the body.

However, that has not generally been the case with brain cancers.

“We haven’t seen much new in treatment for glioblastoma in the past 10 years,” said Dr. Graeme Woodworth, a professor of neurosurgery at the University of Maryland School of Medicine and director of the Brain Tumor Treatment and Research Center at the University of Maryland Medical Center and an active member of the UM Greenebaum Comprehensive Cancer Center. “This is a good study and very promising.”

Brain tumors are notoriously difficult to treat because the immune response in the brain is naturally suppressed.

“The brain is in a closed compartment within the skull,” Woodworth told Healthline. “Swelling can be deadly, so the immune system is designed to limit inflammation and swelling.”

In addition, patients who have been treated with radiation or chemotherapy can have a weakened immune response, and the cancerous tumor produces immunosuppressants that can have an effect not just in the brain but throughout the body, said Prins.

“Checkpoint inhibitors have not worked well in most glioblastoma patients in past few years, whether it be a single agent or in combination with radiation or chemotherapy,” said Dr. Santosh Kesari, a neuro-oncologist and chair of the department of translational neurosciences and neurotherapeutics at the John Wayne Cancer Institute at Providence Saint John’s Health Center in California. “This study, if confirmed in a larger cohort, may allow us to use these drugs in a way that could result in a more robust immune response in the tumor and lead to improved survival.”

“This is the first hint that immunotherapy can have a clinical benefit for patients with malignant brain tumors — and help prevent future recurrences,” added Prins, who is also affiliated with the Parker Institute for Cancer Immunotherapy.

The study involved 35 patients. Of these, 16 received pembrolizumab before surgery and 19 received the drug afterward.

Researchers hope the findings will help determine which immunotherapies work for different types of patients.

Cloughesy, Prins, and their colleagues are now studying the effectiveness of pembrolizumab with other types of immunotherapy drugs and vaccines.

Future studies also may look at whether immunotherapy could take the place of chemotherapy and radiation treatment for glioblastoma.

Woodworth noted that other researchers, notably Carl June, PhD, a professor of immunotherapy at the Perelman School of Medicine at the University of Pennsylvania, have experimented with injecting T cells directly into tumor sites.

Dr. Nader Sanai, a neurosurgical oncologist at the Ivy Brain Tumor Center at the Barrow Neurological Institute in Arizona, told Healthline that using pembrolizumab to treat glioblastoma is a good candidate for a so-called phase 0 clinical trial.

That’s a study that looks at the effects of novel treatments on individual patients (such as shrinking tumors) rather than a statistical analysis of outcomes among a group of patients.

“With glioblastoma, every patient is a little different than the other,” he told Healthline. “We want to see, from patient to patient, what is happening to the tumor,” to target immunotherapy drugs — or a combination of treatments — where they will be most effective.

Immunotherapy drugs such as Keytruda given to brain cancer patients before tumors are removed appear to be more effective than treating patients after tumor removal.

Researchers think the preemptive treatment may help trigger an immune response against cancerous cells.

The study is a ray of hope for the treatment of glioblastoma, a deadly form of cancer with few effective treatment options.

More research is needed to confirm the findings of the small study and to determine what types of immunotherapy work best for individual patients.



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