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Exciting Progress in Treatment of Low-Grade Gliomas

Recently, one of our neuro-oncology faculty, Joe Mendez, MD, took part in a global trial (spanning 10 countries) as the principal investigator here at Huntsman Cancer Institute, which was the fifth top-accruing site and contributed significantly to the study. The trial studied the effects of vorasidenib in low-grade (Grade 2) isocitrate dehydrogenase (IDH)-mutant gliomas. With the first positive result in a phase 3 clinical trial related to brain tumors in the past few decades, as of July, the drug has been fast-tracked for FDA approval.

Low-grade gliomas often affect people in their 30s and 40s who are otherwise healthy.

Dr. Joe Mendez

The tumors grow slowly and are treated with surgery, if amenable, and eventually radiation therapy and chemotherapy. Unfortunately, these gliomas are not curable with current therapies and continue to grow despite efforts to stop, remove, and cure them.

Vorasidenib is an oral inhibitor of a specific enzyme, IDH, that is unique to some low-grade gliomas. The study found that vorasidenib improved progression-free survival (the median time it took for the disease to worsen) and delayed the time to the next intervention in patients with grade 2 IDH-mutant glioma. The results of the study highlight the benefits of the medication: the 168 patients who received vorasidenib had longer control of their tumor than those who received a placebo.

Progression-free survival was approximately 27.7 months for people taking vorasidenib vs. 11.1 months for those receiving a placebo. The time to next intervention was also much better for the vorasidenib group than for the placebo group, and the likelihood of being alive and not needing treatment intervention by 18 months was 85.6% for patients receiving vorasidenib vs. 47.4% for patients receiving a placebo. By 24 months, the likelihood of being alive and not needing intervention was 83.4% for vorasidenib and 27.0% for placebo. Patients who received the placebo were able to switch to vorasidenib if their tumor progressed during the course of the study.

Not only did patients taking vorasidenib compare favorably with those taking a placebo, but they also tolerated the drug very well and typically only experienced low-grade toxic effects, which is an incredible stride. This treatment paradigm could have prolonged quality-of-life effects, because it isn’t as harmful as other treatments and could delay the toxic effects of radiation and chemotherapy.

This kind of medication is the opposite of “one size fits all” and is instead tailored precisely to each individual. Doctors take into account the unique genetic make-up of the patient’s tumor as well as other factors. Tailoring the medication allows doctors to target the genetic changes of a tumor that lead it to become cancer, in the hopes that this will effectively treat the cancer. 

That the study included more than 300 patients at the height of the COVID-19 pandemic is a testament to the dedication and determination of both the patients and physicians to find better therapies for brain tumor patients.