New Standard Of Care Emerges in Anaplastic Glioma

van den Bent, professor, Neuro-Oncology, Erasmus MC-Daniel den Hoed Cancer Center, presented results from the phase III CATNON trial investigating the benefits of adjuvant temozolomide combined with radiation therapy. The combination showed 5-year survival rates of 56%, compared to survival rates of 44% in patients who did not have the addition of temozolomide. The combination also delayed disease progression by more than 2 years and the median time to disease progression was more than twice as long.

In an interview with Targeted Oncology, van den Bent discusses the impact the combination will have on the treatment paradigm for patients with anaplastic glioma, as well as what the CATNON study succeeded at versus its predecessors.

TARGETED ONCOLOGY:Can you give us an overview of the CATNON trials?  

van den Bent:

The CATNON trial was a multi-group trial conducted by EORTC, NRG, NCIC, and MRC, and it investigated the role concurrent and adjuvant temozolomide in patients with 1p/19q co-deleted anaplastic glioma. We started this study back in 2005 when the observation was made that concurrent and adjuvant temozolomide improved survival in glioblastoma. That is typically a chemotherapy-resistant disease. Nonetheless, we saw an increased survival.

On the other hand, we also saw no benefit in (I have no idea what he says here), despite the fact that that is a chemotherapy-sensitive disease. We also noticed in that study that the outcome of patients without 1p/19q co-deletion was signficantly worse than patents with 1p/19q co-deletion, and that is exactly the chemotherapy-sensitive group.

We asked ourselves whether adjuvant or concurrent temozolomide would improve survival in patients without 1p/19q loss with anaplastic glioma. We set up a trial to investigate this. This was a 2x2 design where we first asked the question of if concurrent temozolomide would make a difference, and then asked the second question on whether adjuvant temozolomide would make a difference. That was a trial design that required 750 patients, and we realized that we need to collaborate across continents to make the trial possible.

In 8 years we enrolled 750 patients, and we screened 1400 patients. We were awaiting the outcome of the study to happen in 2022 or 2024, but very much to our surprise a planned interim analysis for efficacy turned out to be positive. This interim analysis was done after 41% of events had occurred. At that time, enrollment was already completed, and very much to our surprise, the IDMC recommended us to release the data on adjuvant temozolomide.

They noticed that 5-year survival increased from 44% in patients without adjuvant temozolomide to 56% of patients that were treated with adjuvant temozolomide. That's a huge increase. This reflects a hazard ratio of 0.64 and a P value of 0.003. That means that adjuvant temozolomide should be part of the standard of care for these patients, even after radiation therapy..

TARGETED ONCOLOGY:What questions still remain?  

van den Bent:

We do not know what the role of concurrent temozolomide is. Part of this treatment is still blinded and we do not know the answer to that. We need to follow the patients further to get those answers. We also do not know at this point in time what the impact of IDH mutational status is. That was something that has to be explored further, but will also require the data from the concurrent part of the study for a full understanding. Although we have the initial results now, it will take a couple of more years before we have all the details there for a final recommendation for our patients.

TARGETED ONCOLOGY:What do you hope community oncologists might take away from these data?  

van den Bent:

Adjuvant temozolomide is now a part of the standard of care for these patients, and probably also is the case for patients with low-grade 1p/19q co-deleted tumors. That is a sizeable proportion of patients that are currently now treated in a lot of areas with PCV chemotherapy in the adjuvant setting based on the other US trial, and we all know that PCV causes more toxic side effects. Especially on the bone marrow, as opposed to temozolomide.