Researchers at Duke University have recently revealed the results from a Phase 1 clinical trial investigating the efficacy of an experimental treatment using a genetically modified poliovirus to attack a lethal form of brain cancer. The results are mildly promising but don't suggest this will be a magic bullet of a treatment.

Glioblastoma is a viciously aggressive form of brain cancer. Even with current treatments, most patients rarely survive longer than a year after diagnosis, and only four percent will survive longer than three or four years.

A team of Duke University researchers has been working on a novel treatment utilizing a custom genetically engineered virus called PVSRIPO. The chimeric virus, a hybrid of poliovirus and rhinovirus, is delivered directly into a brain tumor and stimulates the immune system into a targeted response. In 2016, the FDA designated PVSRIPO a "breakthrough therapy", accelerating its progress into clinical trials.

The results of the first phase of clinical trials have recently been revealed, and while they are somewhat promising, questions remain over the ultimate efficacy of this experimental treatment. The trial ran from 2012 to 2017 and included 61 patients. The treatment group was compared to a historical control group collated from data describing patients suffering the same type of brain tumors but undergoing a more conventional treatment.

Perhaps the most impressive datapoint from this early trial is the long-term survival rate. Those patients undergoing the experimental treatment displayed a 21 percent three-year survival rate, compared to the historical control that showed just a four percent survival rate at three years.

But digging a bit deeper into the data certainly begins to raise some doubts over the efficacy of the treatment. The median overall survival rate of all 61 subjects in the trial was 12.5 months. The median survival rate of the historical control group was 11.3 months. In fact, for the first 18 months of follow up after the trial, patient survival rates in both groups were relatively similar. This means the majority of patients in both the experimental and control groups were dying at the same rate.

After two years, only eight of the 61 subjects in the experimental trial were still alive. These eight patients were still alive at the three-year study cut off date, hence the final long-term survival statistic, but it is noted that as of 69 months following PVSRIPO treatment, only two patients remained alive.

"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," says Andrew Lassman in an interview with STAT. Lassman is a neuro-oncologist and did not work on this new research. "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."

Lead author on this new study, Annick Desjardins, suggests the next stage of human trials will work to address combining the poliovirus treatment with existing therapies to see if that improves survival rates.

"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," says Desjardins. "The big question is, how can we make sure that everybody responds?"

The treatment is currently entering larger, more comprehensive Phase 2 trials, so hopefully it demonstrates better efficacy over the new few years of experiments.

The new study was published in the New England Journal of Medicine.

Source: Duke Today

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