Vorasidenib vs. Radiation — Treating Low-Grade Newly Diagnosed Gliomas

“Going back to the patient who’s newly diagnosed and trying to talk with a patient and decide with a patient. What should we do? Should we do Vorasidenib? Should we do radiation and chemotherapy?” These are important conversations for patients and their doctors to have together, he says.

Understanding Low-Grade Gliomas

Low-grade gliomas (often referred to as Grade 1 or Grade 2 gliomas) are tumors that grow slower than high-grade gliomas. Despite their slower growth, these tumors can still significantly affect quality of life depending on their size and location in the brain.

The tumor’s position in the brain can determine whether a full surgical removal is possible or if a more limited operation or even just a biopsy (obtaining a small tissue sample) is safer.

Many low-grade gliomas also carry mutations in the IDH1 or IDH2 genes. These mutations alter the way tumor cells process energy, contributing to their growth. Researchers have been studying drugs that target these mutations to see if they can slow tumor progression and, importantly, postpone the need for more invasive treatments such as chemotherapy or radiation — and Vorasidenib has shown a lot of promise.

The Role of Radiation in Low-Grade Gliomas

Radiation therapy uses high-energy beams (often X-rays, but sometimes protons) to destroy tumor cells or keep them from growing.

For low-grade gliomas, radiation may be recommended if:

• A tumor is large or causing symptoms that significantly impact daily life
• The tumor shows signs of growing faster than expected
• Surgery wasn’t able to remove a substantial portion of the tumor

Radiation therapy can be very effective in controlling tumor growth. However, it also exposes surrounding healthy tissue to radiation. Over time, this can lead to side effects like fatigue, skin irritation, or—less commonly—cognitive changes. For many patients, balancing the benefits of radiation against its potential long-term effects can be challenging.

Radiation has long been a cornerstone of glioma treatment. But Dr. Peereboom explains that it’s not always an easy decision.

“Radiation treatment carries its own side effects. Many people do not want to have radiation treatment to their brain despite the fact that it does have a longest track record for treatment of grade two gliomas,” he explains.

Radiation: What to Expect

To prepare for surgery, you’ll typically undergo a CT or MRI scan to map the tumor precisely. A custom-fitted mask may be created to ensure your head remains still.

Radiation is usually given five days a week for several weeks. Each session is painless and lasts only a few minutes.

Common side effects include:

• Mild to moderate fatigue
• Localized hair loss
• Occasional skin irritation in the treated area.

Most of these are temporary or manageable with your care team’s support.

Dr. Peereboom stresses that the tumor size and location can also help determine if radiation is the best path.

“If a patient has maybe a small tumor that’s close to the edge of the brain, radiation to that tumor is a lot different than a big tumor that’s in an area that conducts speech,” he explains. “There are different considerations that we have to think about with our patient as to making that decision.

“There are clinical trials now, a number of trials that are in progress to answer these sorts of questions. It’s going to take some time before we know those answers. But those are the questions that we are asking right now.”

Another Option: Vorasidenib

Vorasidenib is a targeted approach, and may help patients avoid the harsh side effects associated with chemotherapy and radiation. However, there are limitations.

“As far as Vorasidenib, I think it’s an excellent drug. However, there are issues with it. We, for instance, don’t really have a good idea as to how it might work for patients who have already had some other treatment like radiation, like chemotherapy,” Dr. Peereboom explains.

Vorasidenib (brand name Voranigo) is a medication specifically designed for patients whose gliomas have mutations in the IDH1 or IDH2 genes. Instead of using broad methods to kill cancer cells (as chemotherapy or radiation might), Vorasidenib zeroes in on the mutated enzymes driving the tumor’s growth.

This targeted approach can potentially:

• Slow tumor progression
• Delay the need for more invasive treatments such as radiation or chemotherapy

Because it’s an oral medication, Vorasidenib also offers a more convenient form of therapy compared to intravenous infusions.

The INDIGO Trial: What We Know

A major study called the INDIGO trial looked at Vorasidenib’s effectiveness in patients with IDH-mutant gliomas and found:

• Patients taking Vorasidenib had a 61% reduced risk of disease progression or death compared to those on a placebo.
• They also had a 74% reduced risk of needing a “next intervention” (like radiation or chemotherapy) or dying from their disease.

These findings are significant because they suggest Vorasidenib can help patients postpone more intensive treatments—and their associated side effects—while still controlling tumor growth.

However, Dr. Peereboom explains that not all patients may be eligible for this new drug.

“The patients in this trial were required to have not had any treatment for at least a year from the time that they had their original surgery. That’s kind of a different group than patients who we might think right upfront need to get some treatment, so the trial really did not address that question,” Dr. Peereboom explains.

Who Qualifies for Vorasidenib?

Vorasidenib is indicated for adults and pediatric patients 12 years and older who have Grade 2 astrocytoma or oligodendroglioma with an IDH1 or IDH2 mutation. Typically, these patients have undergone surgery (including biopsy, sub-total resection, or gross total resection) but have not yet needed, or wish to delay, radiation or chemotherapy.

If you or your loved one fits this category, your care team may recommend genetic testing of the tumor to confirm the IDH1 or IDH2 mutation.

Potential Side Effects

While Vorasidenib is generally better tolerated than many traditional cancer treatments, it can still cause side effects, such as:

• Fatique
• Nausea
• Headaches

Your healthcare team will monitor for any changes in liver function or other potential issues through blood work and regular check-ups. If you experience new or worsening symptoms, it’s crucial to discuss them with your doctor right away.

Vorasidenib vs. Radiation: Making a Decision

For decades, radiation therapy has been a mainstay of glioma treatment. Many patients benefit from it, and it can be a powerful tool in controlling tumor progression. However, Vorasidenib offers a way to delay—or in some cases avoid—the short- and long-term side effects of radiation, especially in younger patients or those concerned about cognitive and quality-of-life impacts.

To make treatment decisions, it’s important to understand how each approach works.

Vorasidenib

• Mechanism: Targets specific IDH1/IDH2 mutations to slow tumor growth
• Delivery: Oral medication
• Ideal Use: Grade 2 IDH-mutant gliomas to delay further interventions
• Common Side Effects: Mild fatigue, nausea, headache, possible liver enzyme changes
• Long-Term Considerations: Potential to postpone chemo/radiation-induced side effects

Radiation Therapy

• Mechanism: High-energy beams to kill or damage cancer cells
• Delivery: Outpatient sessions over several weeks (usually 5 days/week)
• Ideal Use: Can be used for various glioma grades, often after surgery
• Common Side Effects: Fatigue, hair loss in the treatment area, skin irritation
• Long-Term Considerations: Possible cognitive effects, rare cases of radiation necrosis

Every patient’s situation is different. Factors like tumor size, location, grade, and genetic markers all play a role in deciding whether to start with Vorasidenib or move more quickly to radiation. It’s also possible that radiation therapy will still be necessary in the future, even if you choose to begin with a targeted approach like Vorasidenib.

When making the decision, your doctor will consider:

• Extent of surgical resection: Was the tumor fully removed, or did significant tumor tissue remain?
• Patient’s age and overall health: Younger patients might benefit more from delaying radiation, which can have long-term effects on cognition.
• Tumor growth rate: Even low-grade gliomas vary in how quickly they progress.

Questions to Ask Your Doctor

If you or a loved one has been diagnosed with an IDH-mutant low-grade glioma, here are some key questions to ask your medical team.

• Do I qualify for Vorasidenib based on my tumor’s genetic profile?
• What are the potential benefits of starting Vorasidenib now versus waiting?
• How does radiation therapy fit into my overall treatment plan?
• What can I expect in terms of side effects or lifestyle changes?
• Are there any clinical trials available?

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