Vorasidenib Boosts Progression-Free Survival in IDH-Mutant Glioma

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Phase 3 findings showed that vorasidenib improved progression-free survival and time to next treatment in patients with IDH-mutant glioma.

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Vorasidenib improved progression-free survival and time until the next treatment was needed in patients with IDH-mutant glioma, research found.

Vorasidenib (AG-881) is promising new drug for patients with grade 2 IDH-mutant gliomas, a type of brain cancer that typically affects younger people, according to findings from the phase 3 INDIGO clinical trial that were published in the New England Journal of Medicine.

If the drug receives Food and Drug Administration (FDA) approval, it would be the first targeted therapy for IDH-mutant grade 2 glioma, fulfilling a need in a patient population that typically has a poorer prognosis than individuals with grade 2 glioma that does not harbor an IDH mutation.

“There are still many unanswered questions about how we can best utilize this new medication if and when it receives FDA approval,” Dr. David Schiff, co-director of UVA Cancer Center’s Neuro-Oncology Center, said in a press release. “Nonetheless, considering that existing standard therapies for these tumors (radiation and chemotherapy) are tough on patients, with short- and long-term side effects, it will be wonderful to have a useful and very well-tolerated treatment option.”

Vorasidenib is a drug that is taken orally and can penetrate the blood-brain barrier. The agent works by inhibiting IDH1/2, which are proteins sometimes found on gliomas. These enzymes play a role in the growth and development of cancer cells.

The study included 331 patients with IDH-mutant glioma that had been surgically resected. Participants were randomly assigned to receive either vorasidenib (168 patients) or placebo (163 patients). At an average follow-up of 14.2 months, a total of 226 patients were still receiving their assigned treatment.

Findings showed that vorasidenib significantly improved progression-free survival (time from treatment until disease worsening or death) over placebo, with averages of 27.7 months compared with 11.1 months. Additionally, patients in the vorasidenib also had a longer time, on average, until they needed another treatment, such as chemoradiation, which can come with significant side effects that decrease patients’ quality of life. In particular, at the two-year mark, 83% of patients in the vorasidenib group did not need another treatment, compared with 27% in the placebo group.

READ MORE: Vorasidenib May ‘Change the Treatment Paradigm’ for Low-Grade Glioma

These findings, according to Schiff, were “striking.”

“It used to be that we thought of all gliomas as being on a spectrum,” Schiff said. “We now understand that those with the IDH gene mutation have a markedly different biology, outcome and, as this study shows, vulnerabilities that new therapies can exploit.”

According to the release, approximately 2,500 individuals are diagnosed with grade 2 IDH-mutant glioma each year in the United States, with the average age of diagnosis being 40 years — that’s younger than 66, which is the average age of patients diagnosed with cancer across the United States, according to the National Cancer Institute.

Moderate to severe (grade 3 or higher) side effects occurred in 22.8% of patients in the vorasidenib group, compared with 13.5% for those who were in the placebo group. Of note, grade 3 or higher increased alanine aminotransferase, which can indicate damage to the liver, occurred in 9.6% of patients who received vorasidenib.


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