IGCS 2012 - Vancouver, BC, Canada

AURELIA trial, palliative chemotherapy with bevacizumab in resistant, recurrent ovarian cancer

Dr Gunnar Kristensen – Norwegian Radium Hospital, Oslo, Norway

Gunnar, we’re privileged to have you here to talk about this study, the AURELIA trial. Now this is looking at a very special group of patients with ovarian cancer because they have resistant recurrent disease. These patients are in a bad way, what were you doing for them?

What we were doing was to try to prolong their survival and give them relief of symptoms. We did that in a randomised trial where we tested the standard treatment, which is palliative chemotherapy, and in the testing we added bevacizumab which has been shown to slow down the growth of the tumour, both in first line and in the recurrent situation in patients with a late relapse. The population we have evaluated here are patients where the disease recurred very early after stopping chemotherapy. We know that these tumours are really difficult to treat because they usually progress relatively soon even with new chemotherapy treatments.

OK, so what happened in the study?

What we saw in the study was that when we gave bevacizumab together with the chemotherapy, a longer time went before the tumour progressed compared to when we gave just chemotherapy. So we could prolong the time until the tumour started to grow again. And in addition to that we also showed that patients who had fluid in the abdomen, so-called ascites, they had really, really good relief because we did not need to do any drainage of the ascites during treatment with bevacizumab while that was quite common in the group of patients who just received chemotherapy.

So there was an improvement in progression free survival, can you put the data on that? Can you tell me what the figures were?

It was nearly a doubling of the time from about 2½ months on average to about 5-6 months when we added bevacizumab to chemotherapy.

So was there a downside from the bevacizumab? What about side effects?

There are really little side effects. A well-known side effect of treatment with bevacizumab is hypertension so we did see that to some extent, a little bit less than 20% of patients. Usually that is easy to treat so it is not a major problem.

And how significant or how big was the control of the ascites that you found in this group of patients?

There was really good control of the ascites, in fact it was complete control. There were 59 patients receiving chemo and bevacizumab and none of these patients needed any drainage after they had received the first dose of bevacizumab. This is compared to the chemotherapy alone group of 54 patients where 18% of them needed drainage during treatment. So there was a marked difference.

A marked difference indeed. You had, of course, only 179 patients, not a huge study.

That is correct.

But did you feel there was any kind of impact, potentially, on overall survival?

We don’t know yet. We are collecting data on that and will be able to show the effect on overall survival next year. We will aim the presentation at ASCO next year.

Of course, another issue would be quality of life, you’ve talked about the ascites, do you think with a bigger study it would be worth looking at quality of life issues, adding this biologic to chemotherapy?

Yes. We will look into that. We have done that to some extent but we need more time and more work to fully understand the data. So we are looking at that and we’ll come back on that.

Of course there are dilemmas, aren’t there, because these are patients who are going to die and this is palliative therapy. So you’re talking about adding two very powerful agents, what are your thoughts about that?

Give any kind of treatment to these patients, you must be very careful that you really help the patient and not give treatment that adds to their problems. With chemotherapy there is a risk that you add problems also because it’s only a relatively few percentage of these patients, about 10-15% of these patients, where you will see a shrinkage of the tumour with chemotherapy. So just with chemotherapy, that’s a risk that you decrease their quality of life. Here it’s really positive that at least for patients who have ascites you could see there was a good effect and ascites is a thing that gives problems with fatigue, swollen abdomen, decreased appetite, vomiting and also quite many have a pleural effusion giving dyspnea. So to relieve this will automatically be a really good thing for the patients.

Of course it is also good for the patients to have the doctors still taking a great interest in them.

Absolutely.

So what did the patients themselves say about this? Maybe there’s a bit of a trade-off here, they’d like to have treatment because they want to have hope but did they have problems with the treatment?

In the study you pay the same attention to patients in both arms so all patients in the study had quite a high degree of attention. So we will not be able to… it’s not likely that you will see any difference there.

And in the two arms, what was the comparison like between their experience with the two therapies from the patients’ point of view?

We do not have data on the quality of life yet. From my personal experience with the patients in my side, they have been happy with especially the treatment containing bevacizumab and especially if they had ascites because the relief of ascites is a very good thing for the patients.

So what would be the messages coming out of this that doctors should bear in mind when looking at their own patients with resistant, platinum resistant, recurrent disease?

It is important to bear in mind that the AURELIA study is the first study to show a real prolongation of at least progression free survival with any kind of treatment in this patient group. And, for the subgroup of patients with ascites, we have this great reduction of ascites, reduction and the relief of need for drainage of ascites and that’s very important for this patient group.

Gunnar, it’s great to have you with us here on ecancer television.