An inactivated form of the poliovirus used to treat recurrent brain tumors is showing what researchers called encouraging long-term survival in a Phase 1 clinical trial published Tuesday.

The authors reported that 21 percent of patients were still alive three years after the recurrence of glioblastoma, an aggressive and quickly lethal form of brain cancer that is stubbornly resistant to treatment—even the new crop of immunotherapies have proven to be ineffective. Against that bleak backdrop, the early results suggest the experimental poliovirus therapy, invented at Duke Cancer Institute, has some promise.

There are enough caveats in the study design and weaknesses in the new data to raise doubts, however, about whether the therapy—featured twice already on the CBS news show “60 Minutes”—will live up to the hype. A definitive answer will come only after larger clinical trials.

“This is a devastating disease where the prognosis and outcome for patients is very poor, so for us to see long-term survivors with this new treatment is real and very encouraging,” said Dr. Annick Desjardins, director of clinical research at Duke’s brain tumor center and an investigator in the poliovirus therapy study.

Dr. Andrew Lassman, chief of neuro-oncology at NewYork-Presbyterian Columbia University Medical Center, is more skeptical after reviewing the results at STAT’s request. Lassman was not involved in the study.

“I encourage any research in this area that could yield better outcomes, particularly because existing treatments for glioblastoma are so ineffective for patients,” he said. “This [poliovirus] therapy may turn out to be great, but the data are not there yet to conclude that this is the best approach to take.”

The Phase 1 data were presented at the 22nd International Conference on Brain Tumor Research and Therapy in Norway and simultaneously published in the New England Journal of Medicine.

In the study, 61 patients with recurrent glioblastoma were treated with a poliovirus vaccine modified to preferentially target a protein found on brain tumor cells and set off an immune response. Surgeons implant a catheter through the skull of the patients so the modified virus—also known by its scientific name PVSRIPO—could be infused directly into their brains to reach the tumor.

At first, the Duke doctors planned to gradually increase the dose during the study, but at higher doses, patients began experiencing brain swelling that resulted in seizures and cognitive disturbances. The researchers retreated to a lower, safer dose of the therapy, which was eventually used by a majority of the patients in the study.

For all 61 treated patients, the median overall survival was 12.5 months. The study lacked a true control arm, so for a comparison, Duke combed its medical records of past patients to compile a group of 104 with the same type of recurrent glioblastoma. The median overall survival in this historical control group was 11.3 months.

The difference in median survival of slightly more than one month favored the poliovirus therapy over the historical control, but it was not statistically significant.

Researchers also performed an analysis to determine the percentage of patients alive at certain time points.

At one year, 54 percent of the poliovirus patients were alive compared to 45 percent of the historical control patients. At 18 months, 23 percent of patients in each arm of the study were alive.

After 18 months, the Duke researchers say a small group of poliovirus patients began to show signs of extended survival. At two years of follow-up, 21 percent of the poliovirus patients remained alive compared to 14 percent of the control patients.

At three years, the survival gap widened further, with 21 percent of the poliovirus patients still alive compared to just 4 percent of the controls.

“Similar to many immunotherapies, it appears that some patients don’t respond for one reason or another, but if they respond, they often become long-term survivors,” said Desjardins, who has a patent on the poliovirus therapy and owns stock options in Istari Oncology, a company seeking to commercialize the treatment.

But researchers at this point are unable to identify in advance which patients will respond and become part of this group of so-called “long tail” survivors. That group of long-term survivors is also very small, which raises questions about the findings’ reliability. At two years, only eight of the 61 poliovirus patients were still alive and accounted for in the survival analysis. (Some patients were censored, meaning their status in the study is not known.)

“When you look into the details of the poliovirus survival analysis, a one-month median survival compared to Duke’s historical control doesn’t look that great,” said Lassman. “They draw a lot of attention to the cases of long-term survival, but most cancer trials have a similar long tail. It’s not clear whether these long-term survivors were specifically benefitting from this treatment.”

The next clinical trial of the poliovirus therapy is not likely to settle this important survival question. In this Phase 2 study, which recently got underway, patients with recurrent glioblastoma will be randomized into two groups. One group will receive the poliovirus therapy and chemotherapy; the other group will receive poliovirus alone.

That means the study, when completed, will determine if adding chemotherapy to the poliovirus therapy is better than using the poliovirus therapy alone, but it won’t answer the question about whether or not the poliovirus therapy is effective on its own.

Dani Bolognesi, CEO of Istari Oncology, the privately held biotech company that licensed rights to the poliovirus therapy from Duke, said the Phase 2 study was set up by Duke based on positive results from an earlier patient who responded well to the combination approach to treatment.

Bolognesi, a co-author of the Phase 1 study, said the company is working with the Food and Drug Administration to plan additional studies that might compare poliovirus therapy against a standard of care. However, the company is concerned that glioblastoma patients will refuse to participate in such a study because standard-of-care treatments that would be used as the control arm are ineffective.

Republished with permission from STAT. This article originally appeared on June 26, 2018