There has been a lot of noise about the INDIGO trial – it is one of the only trials that has met its primary endpoints before the end of the trial, so the trial has been unblinded and those patients who were on the placebo arm are now receiving vorasidenib. This article explains what this means for patients, what the findings were, which patients were included, how it was designed and what happens next.
A patient experience
Craig has been taking part in the trial and has shared his experience:
I found out about this trial via the brainstrust monthly meet ups. I was so lucky to get onto one of the last spaces on the trial and am forever grateful for this.
From a personal point of view, I have gone through regime. I was on the placebo and had some marginal growth. The trial was unblinded due to the success in data and now I’m on the real drug; my scan looks good so far. It does entail monthly visits with a load of tests every month and sitting in a cancer ward with other people mainly on drips so does make you still feel like a patient but I try to take the positive out of this by seeing the other options over taking a tablet daily and also enjoy speaking to other patients who are various trials for other types of cancer.
The clinical team at Edinburgh Cancer Centre has made the journey easier and its support from clinical care to advice on life decisions has been brilliant and make the monthly visits has positive as possible.
Craig is happy to be contacted via his Instagram handle: craigwright83
What does this mean for patients?
For people with grade 2 glioma with IDH mutations, vorasidenib improves progression-free survival and quality of life. The results of this trial offer a chance to change the treatment paradigm for this type of glioma and could bring the first new targeted therapy for low-grade glioma.
What did the study find?
The phase III INDIGO study showed that vorasidenib may help some people with grade 2 glioma live longer without tumour growth. Vorasidenib targets specific genetic changes called IDH mutations that are commonly found in grade 2 gliomas, which mainly affect people who are young and otherwise healthy. It showed that Vorasidenib delays disease progression in grade 2 glioma with an IDH mutation by an average of 27.7 months, compared to 11.1 months for those taking a placebo. Additionally, vorasidenib delayed the need for the next treatment.
Which patients were included?
80% of patients diagnosed with grade 2 glioma have an IDH1 mutation and 4% have an IDH2 mutation. Current treatment options include intensive treatments with surgery, radiation therapy, and chemotherapy that have short-term and long-term side effects that affect quality of life or an active surveillance approach.
The study included 331 people with grade 2 glioma with IDH mutations who had undergone surgery but no other treatment. Participants came from 10 countries, and their ages ranged from 16 to 71.
What was the study design?
Participants were randomly assigned to 1 of 2 groups. The first group (168 people) received a daily oral dose of vorasidenib. The second group (163 people) received a placebo. The treatment cycles lasted for 28 days. The main goal was to see how long it was before the tumour grew, which is called progression-free survival, based on scans with magnetic resonance imaging (MRI). The researchers also looked at the time it took for each patient to need the treatment with traditional therapies.
There were some side effects associated with vorasidenib, including fatigue, headache, diarrhoea, and nausea. Despite these adverse effects, the benefits of treatment with vorasidenib were observed across all patient subgroups.
What happens next?
Vorasidenib was granted fast track designation by the U.S. Food & Drug Administration (FDA) in March 2023. Servier is working to determine timelines for submission of a New Drug Application (NDA) for vorasidenib to the FDA. It is also under evaluation in combination with pembrolizumab an in ongoing phase 1 study in grade 2/3 glioma. It will be a while before this therapy is available in the UK. We would suggest that patients talk with their oncology team.
- Mellinghoff IK, Van Den Bent MJ, Blumenthal DT, et al: INDIGO: A global, randomized, double-blinded, phase 3 study of vorasidenib versus placebo in patients with residual or recurrent grade 2 glioma with an IDH1/2 mutation. 2023 ASCO Annual Meeting. Abstract LBA1. Presented June 4, 2023.
- Mellinghoff IK, Van Den Bent MJ, Blumenthal DT, et al: Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. June 4, 2023 (early release online).