ESGO 2013

Clinical trials, ENGOT and use of bevacizumab against angiogenesis

Prof Christian Marth - Innsbruck Medical University, Austria

Chris, you’re concerned with organising cancer trials in Europe and you’ve got a whole lot of interesting new things coming along. First of all, could you tell me about ovarian cancer, you’ve got an interesting anti-angiogenic agent that you’re looking at, haven’t you?

Yes, I was presenting a whole bundle of clinical trials organised now by the European Network of Gynae Oncology Trialists groups, the ENGOT, and we have now around thirty trials in ovarian, endometrial, cervical and vulva cancer ongoing so that’s quite high activity. I was presenting one trial, the so-called TRINOVA 3 trial in which patients will be randomised between standard chemotherapy or chemotherapy plus trebananib, which is a novel anti-angiogenic agent. Actually this agent has been shown here to be active in the recurrent situation but what we at ENGOT are doing is now to look whether this is also active in frontline therapy.

So you’re taking a lead and jumping straight to front line?

Yes, I think it’s a very important step forward.

Now this is nothing like bevacizumab, is it?

No, it’s a different agent so we understand now that the toxicity might be different so bevacizumab is inducing hypertension, this does not. On the other hand this agent does provoke oedema which bevacizumab does not. So angiogenesis, as we understand nowadays, is not only a process of one molecule, namely VEGF, we have several lines of activity. At the moment it’s unclear which of those agents are the most important ones but I think we’re on the way to understand. Many presentations also in this meeting are looking for that point.

And putting trebananib into frontline therapy, what are your hopes?

Our hope is to improve progression free survival and maybe also overall survival. So that would be an important answer. We are waiting, of course, we have to wait for the results but the trial is enrolling very well; we have now more than 800 patients enrolled in the trial.

You’re also looking at surgery in recurrent ovarian cancer, why are you doing that?

I think it’s a very important point to understand whether surgery in an ovarian cancer patient who recurs has any benefit. This trial is led by the AGO Germany and they performed previous retrospective analyses and they developed an index desktop which helps us to understand what are the best candidates for surgery. We are now randomising patients into surgery or no surgery followed by chemotherapy in both cases to understand whether removing the tumour in the recurrent situation will improve progression free and, of course, also overall survival. I think that’s a very important trial to understand whether what we are mostly doing at the moment is the correct way to perform.

Difficult to standardise, though, isn’t it?

Yes, of course, but we have a very good index to understand what are the candidates who will benefit from surgery. Because the aim of the surgery, no doubt, is to remove all the tumour nodules so we have to remove everything which is visible, no microscopic residual disease, as in frontline also in the recurrent situation, seems to be of great importance. And we have this index produced by the desktop group, by the AGO Germany and this will help us to select those patients.

What’s the evidence you’re basing your study on, then, that there could be a benefit?

We have retrospective analyses showing us that those patients in whom we are able to remove all the tumour have a great outcome. Of course that’s a selection because it’s not a randomised trial but for those patients in whom we are able to remove completely the tumour to no residual disease, their progression free survival and overall survival is amazingly good. So therefore we are looking for this group of patients and then randomise them into the trial.

We’ve been hearing about endometrial cancer here in Liverpool, welcome news because things are happening. You’ve got a study also looking at adjuvant therapy in this setting. What’s the setting and why are you doing that?

As I said before, ENGOT is trying to start this in all entities of gynae oncology and, of course, the situation in endometrial cancer is somewhat disappointing because we don’t have a really good treatment regimen for the stage 1 high risk patient. What we are performing now, and this is a trial which is led by the Scandinavian group, as to randomise those patients into a chemotherapy which is a standard chemo – carboplatin/Taxol versus nothing, only observation. This will help us to answer the question of whether adjuvant chemotherapy is of any help for those high risk stage 1 patients.

And you think it might be?

Yes, for sure.

Again, what’s the evidence for that so far?

We see that endometrial cancer behaves somewhat very similar to ovarian cancer and, of course, we know that they respond to chemotherapy very well if they recur and we know that there are at least sub-groups of patients who have a disseminated disease even if it’s histological stage 1 and only confined to the uterus. So I think it’s very important to look whether we can improve and neutralise those disseminated cells.

You’re painting a very dynamic picture of research here in Europe being undertaken by ENGOT. What kind of message would you leave doctors with all over the world about the scope for improving the outlook in diseases like ovarian cancer and endometrial cancer?

One of the most important messages is that we should include patients in clinical trials and we should try to work together. I think ENGOT is a very good example that we are able to bring together the European groups on one table and to work together and not to do parallel trials which have not the power to show anything but to go together and join one organisation like ENGOT and then to produce a good outcome and this will change the game.

Chris, thank you very much.

It was a pleasure, thank you.