A new targeted therapy has been shown to significantly improve progression-free survival in patients with low-grade glioma. It could mean a possible new treatment for people with this slow-growing, but life-changing, type of tumour.  

The results from INDIGO, an international phase 3 clinical trial, showed that the targeted therapy, vorasidenib, more than doubled progression-free survival in people with recurrent grade 2 glioma.   

Compared with people who received a placebo, those who took vorasidenib went for nearly 17 more months without their cancer worsening. It means patients who took the drug did not need to start chemotherapy and radiation, which have substantial side effects, until much later. 

The delay in starting chemotherapy and radiation is important for patients with the recurrent grade 2 glioma with IDH1 and IDH2 mutations studied in this trial because this subtype of glioma tends to affect younger people, often those in their 30s. The current standard treatment of radiation and chemotherapy can cause neurological deficits that make it hard for patients to learn, remember new things, concentrate or make everyday decisions – all of which can be especially challenging for people with young families or in the early years of their professional lives.   

The researchers from the University of California, Los Angeles found that the disease progressed in just 28% of people receiving vorasidenib, compared to 54% of those receiving placebos. As of September 2022 (30 months after the study began), 72% of patients who were in the vorasidenib group were still taking the drug and their disease had not progressed.   

The results of the trial, published in the New England Journal of Medicine, represent the first clinical trial to analyse a targeted therapy drug specifically developed to treat brain cancer.   

Targeted therapies are designed to target specific molecules that are involved in the growth and spread of cancer cells. Unlike chemotherapy and other therapies that can affect both cancerous and healthy cells, targeted therapies only attack cancer cells with the mutated target while minimizing damage to normal cells.  

Dr Garth Cruickshank, Chair of our Scientific and Medical Advisory Board said: “The INDIGO trial has provided a highly convincing, highly promising and somewhat surprising result.  

“Highly convincing, because it has been performed as a double blinded controlled trial in highly comparable test and control arms with more than adequate numbers of patients.  

“Highly promising in that there is significant prolongation of progression-free survival and delay in time-to-next-intervention with a very manageable safety profile. This latter issue being very important bearing in mind patients would have to take this drug for an extended period.  

“Surprising because, although we understand that the mutant enzymes were inhibited resulting in a suppression of the production of oncogenic stimulator 2-HG, it is the first targeted therapy to show activity in glioma in more than a very limited number of patients.  

“This study is a game changer for our insight into gliomagenesis, but also for all patients who present with IDH mutated glioma, offering significant survival improvement at low cost to their quality of life, and the postponement of damaging radiotherapy. It heralds a new era for these patients” 

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