A genetically modified polio virus improved the longer-term survival of patients with a lethal type of brain tumor, according to the results of an early-stage clinical trial published Tuesday.
Twenty-one percent of the patients treated with the virus — all with disease that had recurred — were alive after three years, compared with just 4 percent of those who had undergone standard chemotherapy.
The trial at the Duke Cancer Institute involved patients with glioblastoma, the kind of tumor that Sen. John McCain (R-Ariz.) is battling. The results were published online in the New England Journal of Medicine and presented Tuesday at an international brain tumor conference in Norway.
Glioblastoma, a difficult-to-treat disease that is the most common of all malignant brain tumors, can cause seizures, headaches, blurred vision and confusion. Even with aggressive treatment, people who are newly diagnosed typically survive less than 20 months, while those with a recurrence usually die within a year.
Duke researchers opened the Phase 1 trial in 2012 to test the safety of the modified-virus treatment and try to determine the right dose. After surgeons implanted a catheter in each patient's brain, a small amount of a genetically modified form of the polio virus was infused directly into the tumor. The virus is designed to target the tumor cells and trigger a response by the immune system.
The approach got widespread attention in 2015 when it was covered by the CBS program “60 Minutes.” The first participant in the trial was a nursing student who has since gotten married and become a nurse, according to Duke officials.
Tuesday's results were welcomed by experts who were not involved in the study. Yet those scientists strongly urged caution, saying it was too early, and the number of patients in the trial too few, to know just how effective the approach is for glioblastoma.
The polio treatment is one of several “oncolytic viruses” being investigated as anti-cancer agents. While researchers have long viewed such viruses as potential tools for directly killing cancer, they now suspect that the viruses might be more effective at marshaling the body's immune system against malignancies, according to the National Cancer Institute.
The Duke researchers said the median survival for the 61 patients in the trial was 12.5 months, compared with 11.3 months for the “historical control group.” The latter is a group of patients, used for comparison, who were treated earlier with standard chemotherapy and met the criteria for the polio virus trial.
A subset of patients who received the treatment and survived at least two years got a much bigger boost.
Debra Puffer, a 61-year-old resident of Rome, N.Y., was diagnosed with glioblastoma in 2014 and was treated with surgery, chemo and radiation. When the cancer came back, she got the polio virus therapy at Duke and went 2½ years without a recurrence. When the cancer returned again, she got a “booster” infusion of the polio virus last August.
She wound up in the hospital with severe side effects. But now, “everything is looking much better,” including her brain scans, she said. “I am enjoying my summer.”
Annick Desjardins, a Duke neurologist who is one of the lead authors of the study, said the polio virus treatment appears similar to other immunotherapies in that the majority of treated patients don't respond. However, those who mount “an active immune response” have the real possibility of becoming long-term survivors, she said.
To try to increase the percentage of such responders, scientists opened a Phase 2 trial at Duke and three other medical centers to test the polio virus treatment plus a chemotherapy drug, vs. only the virus. Researchers also are planning trials for breast cancer and melanoma.
Deepa Subramaniam, director of the brain tumor center at Georgetown Lombardi Comprehensive Cancer Center, called the results “very interesting, enough reason to keep going.” But she noted that it was “a very early-phase trial” and that the treatment needed more scrutiny.
John de Groot, a neuro-oncologist at MD Anderson Cancer Center, called the study “good science” but said the therapy's effectiveness needed to be tested in a much larger number of patients and at many medical centers. Both he and Subramaniam questioned the use of a “historical control group” rather than an actual one. Subramaniam said it was a “suboptimal way to compare” outcomes between patients getting an experimental treatment and those receiving standard therapy.
Desjardins said the study authors decided a traditional randomized trial would have been unethical because those who didn't get the treatment would have been subjected to sham procedures, such as insertion of catheters that did not deliver the virus, so that they wouldn't know whether they were getting the experimental therapy.