The background of the study dates back two decades now because we started discussing this trial back in 2005, 2006. At the time we had a positive study adding temozolomide to radiation therapy in glioblastoma; we had a negative study in adding PCV to radiation therapy in oligodendroglioma and we realised that the patients without the 1p19q codeletion had a worse outcome. So we asked ourselves would the addition of temozolomide to radiation therapy improve the outcome in the patients with anaplastic glioma without the 1p19q codeletion. We wanted to answer basically two questions: whether the addition during radiation therapy would make a benefit and whether the addition of chemotherapy after radiation therapy would make a benefit. So we ended up with a two-question trial with four arms.

Since the start of the trial our landscape has changed, the way we are seeing these tumours has changed because of the IDH mutation. So today I have been reporting on the subgroup of patients with the IDH mutation as this is, from today’s clinical perspective, the most relevant patient group.

What was the methodology?

The methodology was a randomised trial. We randomised the patients into four arms – radiation therapy alone, radiation therapy with concurrent temozolomide, radiation therapy followed by adjuvant temozolomide, and radiation therapy combined with temozolomide followed by adjuvant temozolomide – asking the two questions – adding temozolomide during radiation therapy and adding temozolomide after radiation therapy. A randomised controlled trial, multicentre, multicontinental trial.

What did you find?

The findings were reported before. We have made earlier reports back in 2019, 2021, based on IDMCs that reported first efficacy of the adjuvant part and then futility of the concurrent part. Today we report a more mature analysis based on the analysis primarily on the patients with an IDH-mutated glioma. What we see in that group of patients is that adding temozolomide during radiation therapy doesn’t make an improvement in outcome, all the improvement in outcome is if the temozolomide is given after the radiation therapy and that improvement is really substantial. There is nearly a doubling of the survival time from 5.1 years with radiation therapy alone to over 10 years if you add adjuvant temozolomide to radiation therapy.

What are the clinical implications of these findings?

The clinical implication is that we have more proof of principle of the guidelines that we have. We knew already there was benefit in the IDH-mutated glioma, we see now that there is a longer survival but also with a more mature analysis we are able to look better at the prognostic factors. So we identified a number of prognostic factors that convey a worse survival in patients but we also showed that even in the patients with a worse survival based on those biomarkers there is still the same amount of benefit of adding temozolomide to radiation therapy. So despite the fact that we have identified factors of prognosis, we also show that these poor prognostic factors should not keep physicians away from adding temozolomide to radiation therapy.

Is there anything else you would like to add?

I think this is an important study, it’s a pivotal study. We earlier showed that the addition of chemotherapy in the IDH wildtype tumours didn’t make an outcome. We still do not really expect that. We also showed that MGMT promotor methylation in the group of patients with an IDH-mutated tumour do not have any impact on either the prognosis of patients or a predictive value.