ASCO 2012, Chicago, USA

Combined chemo-radiation extends survival for anaplastic oligodendroglial tumours

Professor Martin van den Bent – Erasmus University Medical Center, Rotterdam, The Netherlands

ecancer.tv now has the privilege of being with Professor Martin van den Bent. Martin, you’ve just been talking about oligodendroglioma and this is a relatively common primary brain malignancy, what’s new about this? You’ve done a study.

Yes, well anaplastic oligodendroglial tumours are about 5-10% of all primary brain tumours. What we have investigated was whether it was better for these patients to get chemotherapy early, immediately after radiation therapy, or whether we should give the same chemotherapy at the time of first progression. What we show is that, despite a crossover that we had in our study, we see a significant clinically relevant increase in survival if we give chemotherapy early on. Survival increases, on average, from 30 months with radiation therapy alone to 42 months with radiation therapy plus PCV.

25%.

Yes, it’s a great increase.

And that, of course, is a 25% improvement then.

Yes, that’s a great achievement, it’s a great achievement. So it’s clear that we have changed the standard of care.

This is triple therapy so you’ve got the surgery, you’ve got the radiotherapy, you’re now saying add the chemotherapy with, in this case, it’s PCV chemotherapy. Tell me a little bit about that please.

It’s a combinational regimen that was developed in the mid ‘80s of the past century which is a combination of procarbazine, CCNU or lomustine and vincristine, all drugs that are very effective, as we have shown.

Now I’ll come back to the alternatives to which chemotherapy you use in a minute, but a deletion, a gene deletion, is quite important here, isn’t it? The 1q 19q deletion, what does that determine?

When we were doing the study it became clear that we already knew that anaplastic oligodendroglial tumours at recurrence were sensitive to PCV chemotherapy. It was shown that in particular those patients with loss of part of chromosome 1 and part of chromosome 19, so-called 1p 19q co-deletion, had a high response rate to this PCV regimen. So we analysed the patients in our study prospectively for 1p 19q loss and what we found is that 1p 19q loss actually predicts the benefit of PCV chemotherapy. We see in that group an almost 45% reduction of death after a follow-up of 12 years, median follow-up is 12 years in the study now. We see overall survival in this 1p 19q correlated group of about 9 years and after 12 years of follow-up we still have not reached the median survival in the ones with 1p 19q correlated treated with PCV. So it’s a huge increase that we are seeing. Interestingly, the increase in survival doesn’t start until after year 6 so there is some biology behind this.

So you’ve established proof of principle about using chemotherapy; you’ve also established a very interesting effect of the genetics of this whole situation. I need to ask you, don’t I, about temozolomide because you’ve got alternative drugs that you could be using, haven’t you?

Yes, since we started this study temozolomide has come to the market and temozolomide has replaced the use of PCV by and large. Most centres are now using temozolomide, not because it’s more effective, there are no randomised controlled trials here, but because it’s better tolerated by the patients. Whether temozolomide is equivalent to PCV, we don’t know; it’s being used, it’s widely being used, most physicians will not use PCV anymore. The question remains on the table whether with the huge increase in survival that we now see with the addition of PCV to radiation therapy, will we get the same bang for the buck if we start using temozolomide.

So what’s the provisional clinical message for busy doctors about oligodendroglioma?

Especially in the ones with 1p 19q co-deletion, standard of care is now radiation therapy plus chemotherapy and one can argue whether it should be PCV or temozolomide but chemotherapy should be part of standard of care in addition to radiation therapy.

So that’s changed?

That has changed.

Thank you very much.

My pleasure.