A Phase III trial in recurrent glioblastoma (GBM) revealed that matching treatment with ChemoID, a stem cell-based diagnostic assay, improved survival over physician-selected treatment. The trial involved GBM patients whose cancer returned after initial treatment. Those receiving treatment recommended by the stem cell test survived an average of 3.5 months longer than those in the physician-choice group. The trial data was published in Cell Reports Medicine.
The trial tested the effectiveness of a platform called ChemoID, a CLIA- and CAP-accredited diagnostic test developed by Dr. Pier Paolo Claudio and Dr. Jagan Valluri of Cordgenics LLC. The test analyzed GBM cancer stem cells that contribute to therapy resistance and cancer progression.
This study included 78 patients with recurrent GBM treated at 13 sites in the US. Patients in the trial were randomized to have the choice of cost-effective chemotherapy treatment decided through ChemoID or to have physicians choose chemotherapy using standard methods. After craniotomy, resected tumor tissue was sent to a CLIA and CAP-certified laboratory. Cancer stem cells were isolated from the tissue. The stem cells were incubated with the various drugs, and the ChemoID assay provided a report of which were more effective. The patients were then treated with the matched drugs or those chosen by the physician, which the researchers note are often dictated by guidelines and insurance considerations.
“We first wanted to design the trial to test its effectiveness against FDA-approved, cost-effective chemotherapies as a proof of concept,” explains Soma Sengupta, MD, PhD, who is co-first author of the research and a University of Cincinnati Brain Tumor Center physician-researcher along with Tulika Ranjan, MD, of Allegheny Health Network in Pittsburgh.
Those who had their treatments selected through ChemoID had a significantly lower risk of death and, on average, survived 3.5 months longer than those in the physician-choice group. In the ChemoID assay-guided group, median survival was 12.5 months compared with 9 months in the physician-choice group.
“These Phase III study results now show that it can be deployed anywhere in the world with commercially-available, cost-effective therapies that are routinely covered by Medicare and health insurance plans,” says Sengupta. “For this patient group, a 3.5-month survival advantage is meaningful.”
The study showed that the assay results were returned within a week after surgery, which Sengupta explains is sufficient as patients need several weeks to recover before a craniotomy could be performed.
The team will next test the platform with a broader range of therapies, including targeted therapies and immunotherapy. In addition, the group plans to expand the platform with other agents to see if it can be effective in the newly-diagnosed GBM setting.
Also, recognizing that matching a single drug with GBM stem cells is unlikely to provide the best survival outcomes, Sengupta suggests that an assay like ChemoID may be best used in combination with other technologies that improve drug delivery.
“The brain barrier is a huge issue in glioblastoma,” she says, so theoretically, one could potentially pair this platform with approaches like therapeutic RNA delivery or others that open it up.
“Even with this assay, it is not a question of just one drug for GBM,” she adds. “It has to be a combination of agents, and also a combination of approaches, because of the uniqueness of the issues with a blood-brain barrier—it’s the potential that it has to work alongside other things that I think makes it a big deal.”
