Who Benefits From Vorasidenib? Understanding Ideal Candidates vs. Real-World Complexity

Creator: Dr. Kaique Filardi
Published: 2025-11-24T19:28:52-05:00

: Dr. Jacob Young Medical Source: Dr. Akanksha Sharma
Sutter Health Written by: Dr. Kaique Filardi
University of São Paulo

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What You Should Know

Vorasidenib is a major advance for grade 2 IDH-mutant gliomas, reducing the risk of progression or death by 61% in the INDIGO trial — but not every real-world patient fits the exact trial profile, which is why treatment decisions must be individualized.
Some patients are excellent candidates for vorasidenib, especially younger adults with residual or subtly growing IDH-mutant tumors who want to delay radiation because of long-term cognitive concerns. But factors like emotional readiness, ability to commit to a daily medication, insurance stability, and access to monitoring all matter.
Patients in the “gray zone” may reasonably choose other approaches, including active surveillance, short-course temozolomide, or early radiation with chemotherapy — particularly when imaging shows higher-risk features or when lifestyle, logistics, or tumor behavior make long-term daily therapy challenging.

The FDA-approved drug Vorasidenib marks a major advance for patients with IDH-mutant gliomas—especially grade 2 tumors. In the INDIGO trial, a Phase 3 clinical trial, it reduced the risk of disease progression or death by 61% and extended progression-free survival (period with stable disease) from 11.1 to 27.7 months. For many patients, that represents a life-changing difference.

But even with such strong data, not every patient fits neatly into the INDIGO trial profile. And this is where the real-world complexity begins. In that sense, there are patients who are perfect matches for vorasidenib, and there are patients who live in the gray zones — where it is unclear whether they would benefit from the drug. That’s where conversations between doctors and patients become highly individualized.

Understanding those gray areas is critical, because more and more patients are asking: “Am I someone who should start vorasidenib now… or is another approach better for me?” And, sometimes, there is no short answer.

Who Is A Match For Vorasidenib?

To answer this question, we should go back to the study that has revolutionized this field: the INDIGO trial, a trial that showed vorasidenib significantly delays tumor progression in patients with IDH-mutant grade 2 gliomas.

This study looked at patients who:

had grade 2 IDH-mutant glioma,
underwent surgery,
had residual tumor or subtle regrowth,
had not yet received radiation or chemotherapy.

“In terms of when we are thinking about who is the best candidate for IDH inhibitor therapy, so ideally it’s firstly a patient who meets the criteria for the clinical trial that was done,” Dr. Akanksha Sharma, a Neuro-oncologist at Sutter House California Pacific Medical Center in San Francisco, California says.

These “classic profile” patients are generally strong candidates for vorasidenib, especially if they’re young and highly motivated to delay radiation because of long-term cognitive concerns.

But even within this group, there are nuances. “If they [patients] cannot take a daily therapy for many reasons or if they feel uncomfortable with that idea of being on something indefinitely because we really don’t know yet how long patients will continue that treatment in those patients, there might still be an option for surveillance or to consider Temodar (temozolomide) for a short period of time or even radiation,” specifies Dr. Sharma.

Some patients struggle with the idea of long-term treatment more than the treatment itself. Others are simply not ready emotionally or logistically for a therapy that requires ongoing monitoring.

Patients Who Can’t Commit to a Daily Drug: Gray Zone

Vorasidenib is oral, convenient, and taken at home. But when patients realize that it is a life-long commitment, with undefined long-term consequences or side-effects, and they may face financial and emotional burden, the conversation changes.

For instance, not everyone lives close to a neuro-center; others may have inconsistent access to lab facilities, or individuals with unstable or high-deductible insurance plans. Additionally, sometimes the workload or family responsibilities make frequent visits difficult or even impractical.

For these patients, doctors sometimes consider:

active surveillance (watchful waiting)
a short course of temozolomide (a pill-based chemotherapy)
delaying treatment until growth is more clearly documented

These are legitimate pathways, not failures or worse choices, and they reflect how medicine adapts to real life.

“It is my goal, and it is every physician’s goal, to have patients live as long as possible,” says Dr. Sharma.

What If I Want to Avoid Radiation?

Another important gray zone involves younger adults with IDH-mutant glioma, people in their mid-adult life who may live with this diagnosis for many decades.

Radiation remains one of the most effective treatments for glioma, but we now understand far more about its long-term trade-offs. Even with highly advanced techniques such as proton therapy or hippocampal-sparing approaches, radiation can still cause subtle cognitive shifts years later, meaning changes in memory, processing speed, or multitasking that accumulate slowly over time. And that’s absolutely something we do need to discuss.

“If I’m expecting this patient to still be here 20, 30 years from now, I have to consider there may be long-term toxicity that I want them to avoid, and that’s when I would advise against radiation, for example, or ask to push out radiation as long as possible,” Dr. Sharma points out.

That’s why many specialists lean toward vorasidenib when they see a younger patient with slowly progressing, residual IDH-mutant disease. The medication offers a chance to delay radiation by years while keeping the tumor under control.

On the other end of the spectrum are patients whose tumors raise red flags: cases where the imaging or pathology suggests a risk that the glioma may evolve into a more aggressive form. These warning or concerning signs can include larger tumors, significant residual disease after surgery, or MRI features that hint at increased cellularity or early transformation. In these situations, waiting carries more risk, and vorasidenib alone may not provide adequate control.

Finding Hope & Meaning: Living Fully with a Glioma Diagnosis

Here, radiation, often combined with cytotoxic chemotherapy like Temozolomide (TMZ), an oral chemotherapy drug that is commonly used to treat gliomas, remains the most reliable approach backed by decades of outcomes data.

Dr. Shamar notes, “If the tumor shows abnormal features or concerning behavior, those patients may benefit from radiation early on with chemotherapy. Waiting may not be safe.”

This group often includes patients whose tumors grow quickly between scans, cause new symptoms, or who have pathology findings that don’t fit the slow-growing profile seen in the INDIGO trial.

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