Cetuximab superior to bevacizumab for advanced colorectal cancer

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Published: 1 Jun 2013
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Dr Volke Heinemann - University of Munich Munich, Germany

Dr Volke Heinemann talks to ecancer managing editor, Prof Gordon McVie, at ASCO 2013 about the German phase III clinical trial FIRE-3.

The study found that first-line cetuximab plus FOLFIRI chemotherapy (folinic acid, fluorouracil, irinotecan) offers a roughly four-month survival advantage for patients with metastatic colorectal cancer, compared with bevacizumab plus FOLFIRI. The targeted drugs cetuximab and bevacizumab, both in combination with chemotherapy, are approved and commonly used as initial therapy. Until this study, it had been unclear which approach is better for patients with non-mutated forms of the KRAS gene.


ecancer's filming at ASCO has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.


ASCO 2013

Cetuximab superior to bevacizumab for advanced colorectal cancer

Dr Volke Heinemann - University of Munich Munich, Germany

Professor Heinemann, thank you very much indeed for giving us really the bottom line of this very important trial that you’ve presented at ASCO. It’s in advanced metastatic colorectal cancer patients who have got wild-type Kirsten ras. What did you do?

We performed a randomised phase III trial comparing FOLFIRI, which is a standard chemotherapy in Germany and also in Europe, plus either cetuximab or bevacizumab as a targeted agent. This was a one to one randomisation in these metastatic KRAS wild-type patients.

How many patients?

592 patients were recruited onto the trial and all of them were KRAS wild-type.

And the bottom line is quite remarkable, is it not?

It is. We have to differentiate, however, a primary endpoint that was not positive. The primary endpoint was objective response rate and in the intent to treat evaluation we find no difference between arms. However, if we look at the accessible patients, which are patients that needed to have received at least three cycles of treatment and needed also to have one imaging procedure to evaluate these patients, in this group of patients we find a significant superiority of the cetuximab arm, roughly 10%. Now the key finding of our trial is, however, an advantage in overall survival of 3.7 months observed in the cetuximab arm, as compared to the bevacizumab arm. So we look at 28.7 months overall survival versus 25 months.

Tell me what the difference is in how the patient received the two arms, differences in toxicity and ability to do things.

I think from a general toxicity standpoint we can say that the toxicity was quite manageable. We find rather low grade 3/4 diarrhoea rates, lower than 15%. We find, however, toxicities which are certainly related to the targeted treatment. Cetuximab induces more skin toxicity which is acneiform rash, for example, nail toxicity and so on while bevacizumab notably induces more hypertension, some wound healing problems, some fistulae and so on. Interestingly with regard to toxicity we have equal rates of thrombotic and thromboembolic events in both arms, that was not expected.

And do you have any idea about the relative costs of the two arms of the trial in terms of euros?

Well, this evades the knowledge of a common physician, as me. I would say this would be the task of a formal pharmaco-economic analysis but that we did not, however, perform.

Is cetuximab the same price as bevacizumab in Germany? I have no idea.

Honestly, I don’t know either because I’m neither interested in that nor responsible for that. I cannot answer that question.

The health authorities, however, who would pick up on your trial and make this the standard approach will want to know how much it costs, certainly in the UK.

Certainly, yes. Mind you, it is rather so in Germany that the survival will be of great importance and if we find survival gains we will pay for that. Specifically in the range that we have observed I think roughly four months survival gain will support a treatment in any case. Almost regardless of the costs also since both agents are registered in Germany.

Professor Heinemann, congratulations on being very patient and accruing very significant numbers of patients and coming out with a really, really elegant result. Well done.

My pleasure. Thank you very much.