Vorasidenib: A Promising Targeted Therapy For Low-Grade Gliomas

“We have progression-free survival data from that trial. We don’t have life expectancy data from that trial, and we’re not going to get real life expectancy data from that trial because patients getting placebo were allowed to cross over at progression. So in the end, every patient got vorasidenib if they wanted it at some point in the time of the study,” Dr. D. Ryan Ormond, a neurosurgeon at the University of Colorado, tells SurvivorNet.

This means that while the drug has shown the ability to slow disease progression, its impact on overall survival is still unknown. Nonetheless, the fact that many patients in the study chose to switch to vorasidenib highlights its perceived benefits.

What is Vorasidenib?

Vorasidenib is an oral medication designed specifically to target low-grade gliomas that have mutations in the IDH1 or IDH2 genes. These mutations are found in the majority of low-grade gliomas and are thought to drive tumor growth by disrupting normal cellular metabolism.

Unlike traditional chemotherapy or radiation therapy, which can have significant side effects, vorasidenib is a targeted therapy — meaning it directly interferes with the cancer’s ability to grow while sparing healthy cells as much as possible. This makes it an attractive option for patients looking for an effective yet less toxic treatment.

However, more research is needed to determine if vorasidenib is a more effective option than other treatments.

“We know that it’s better than no treatment, but we don’t know if it’s better than other treatments,” Dr. Ormond explains. “But I do think it’s a good option for a lot of people.”

How Does Vorasidenib Work?

Normally, IDH enzymes help cells carry out essential metabolic processes. However, when these enzymes are mutated, they produce an abnormal substance called 2-hydroxyglutarate (2-HG), which prevents cells from differentiating properly. This leads to uncontrolled tumor growth.

Vorasidenib works by blocking the activity of mutant IDH enzymes, reducing the levels of 2-HG. As a result, the abnormal tumor cells slow their growth and may even revert to a more normal state. This delay in tumor progression allows patients to postpone or avoid more aggressive treatments.

When is Vorasidenib Recommended?

Vorasidenib is indicated for patients with IDH1 or IDH2-mutant low-grade gliomas that are not rapidly progressing. It is particularly beneficial for those who have been diagnosed with the disease but do not yet require immediate invasive treatment such as radiation or surgery.

In many cases, patients with low-grade gliomas adopt a “watch and wait” approach, where doctors monitor the tumor with regular MRIs.

Vorasidenib offers an alternative to simply waiting, as it actively slows tumor growth and may extend the period before more aggressive treatment is necessary.

What Are the Benefits of Vorasidenib?

The INDIGO Trial demonstrated several important benefits for patients taking vorasidenib, including:

• Longer progression-free survival: The drug significantly extended the time before the tumor began to grow again.
• Delay in the need for radiation or chemotherapy: Many patients who took vorasidenib were able to postpone invasive treatments, reducing the risk of long-term side effects.
• Oral medication: Unlike chemotherapy, which often requires IV administration, vorasidenib is a pill taken by mouth, making it more convenient for patients.
• Targeted approach: The drug specifically attacks the molecular mechanisms driving the tumor, minimizing damage to healthy brain tissue.

What Are the Side Effects?

As with any medication, vorasidenib does come with potential side effects.

According to clinical trial data, some of the most commonly reported side effects include:

• Fatigue: Many patients reported feeling unusually tired while taking the drug.
• Liver enzyme abnormalities: Blood tests showed changes in liver function in some patients, which may require monitoring.
• Nausea: Some individuals experienced mild nausea, although it was typically manageable.
• Cognitive changes: A small number of patients reported issues with memory or concentration, though these effects were generally mild.

It is important to discuss these potential side effects with a doctor to determine whether vorasidenib is the right choice based on individual health status and treatment goals.

What Questions Still Remain?

While Vorasidenib represents an exciting advance in the treatment of low-grade glioma, there are still several unanswered questions, including:

• Does vorasidenib improve overall survival? Since patients in the INDIGO trial were allowed to switch to vorasidenib upon tumor progression, researchers cannot definitively say whether the drug increases life expectancy.
• What are the long-term effects of taking vorasidenib? Since this is a relatively new drug, its long-term impact on brain function and overall health is still being studied.

• How does vorasidenib compare to other emerging treatments? Researchers continue to explore other targeted therapies, immunotherapies, and combination treatments to determine the best approach for managing low-grade gliomas.

What Does This Mean for Patients?

For patients diagnosed with a low-grade glioma, the availability of vorasidenib marks a significant milestone. It provides an option that may slow tumor growth, delay more aggressive treatments, and offer a better quality of life.

If you or a loved one has been diagnosed with a low-grade glioma, discussing genetic testing for IDH mutations with your doctor is an essential step. If your tumor carries one of these mutations, vorasidenib could be a potential treatment option.

The future of low-grade glioma treatment is evolving rapidly, with vorasidenib paving the way for more targeted, patient-friendly therapies. While further research is needed to fully understand its long-term benefits, its approval brings new hope to patients and their families.

Questions to Ask Your Doctor

• Have I been/can I be tested for an IDH mutation?
• Am I a good candidate for vorasidenib?
• Is vorasidenib a better option for me than radiation or chemotherapy?
• What are the benefits of a watchful waiting approach?

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