World Congress on Gastrointesetinal Cancer 14, Barcelona, Spain

Adjuvant cetuximab disappoints again in mCRC

Professor Michel Ducreux – Institut Gustave Roussy, Villejuif, France

What presentations at this meeting have stood out to you?

This meeting is very interesting because we see in this meeting more and more very new data, for instance, concerning metastatic rectal cancer. This morning we have seen the first presentation of the data of the comparison of FOLFOX cetuximab versus UFT oxaliplatin and cetuximab. It was presented by J Y Douillard and it confirms something that we already have seen in other HER studies, I mean that to combine cetuximab with oral drug chemotherapy is not easy and the results were worse when using a combination of the oral 5-FU plus oxaliplatin plus cetuximab versus the standard regimen, FOLFOX cetuximab. The same thing was observed too and presented to Jullian Taieb disease of plus trial and con trial, given interesting data which are positive when you combine oxaliplatin and infusional 5-FU plus cetuximab, it seems to work but if you combine oral drug plus oxaliplatin plus cetuximab, it’s not a good combination and there are some problems of toxicity, maybe interaction, and it doesn’t work.

First results of the PETACC8 trial were presented; can you tell us about that trial?

Yes, about adjuvant treatment in the PETACC8 study, to continue to speak a little bit about the use of cetuximab. It is cetuximab, the evaluation of cetuximab as an adjuvant treatment, it was a comparison of FOLFOX versus FOLFOX cetuximab and the results are totally negative in terms of progression free survival and overall survival. Even if you look only at patients, a little bit more than 2000 patients have been included in that trial, if you select the population of patients, a little bit more than 1,950 patients that were KRAS wild-type, even in that specific population the addition of cetuximab does not change the progression free survival of the patient. So it is a little bit disappointing. It confirms the US trials that have given very, very similar results. The main point now is to go into the details of the biological samples that have been made in the patients in that study and translational research that is around the study will, I hope, give interesting results in the future to select patients, maybe.

Were you surprised by the results of the PETACC8 trial?

I was not surprised by the results of the PETACC8 trial because it has been presented two years ago, the results of the US trial evaluating cetuximab in patients as adjuvant treatment after resection of colon cancer and it was negative. It means that it is complicated, to improve the results in the adjuvant setting we add the results of negative studies with bevacizumab, the addition of cetuximab even in a selected population with KRAS wild-type tumours is also negative. So it means that we continue now to treat patients, we have to continue to treat patients as the standard of care only with chemotherapy – 5-FU, leucovorin and oxaliplatin.

What do these data mean for the adjuvant use of cetuximab?

We will not be able to give cetuximab to patients as adjuvant treatment; we will continue to use cetuximab as it is in first line, second line treatment. It is a very active drug and it has improved clearly the treatment of patients with metastatic colorectal cancer. With translational research that is around these two negative trials, we have the hope to find some very, very specific biological markers that could help us in the future to do a new trial in a very, very much more selected population.

What about the use of newer agents in the adjuvant setting?

In the adjuvant setting the use of newer drugs remains very, very difficult because we have to perform very huge trials now in the adjuvant setting, so trials included a little bit more than 2,000 patients. So, for instance, with the panitumumab, which is another anti-EGFR antibody, the company decided not to go into an adjuvant trial because they considered that it’s a lot of money and probably no clear results at the end. So improvements in the setting of adjuvant colon cancer remain very, very, very slow and we are a little bit disappointed at this time.

How can clinicians choose between all the different molecularly targeted agents now available for mCRC?

The choice between the different types of targeted therapies that are on the market is clearly a little bit difficult at this moment. It is quite simple in patients with mutated KRAS tumours because if you want to give targeted therapy to these patients the only choice is to use bevacizumab. In that situation it’s quite simple. In patients with wild-type tumours you have a larger choice, you may use bevacizumab also but it is possible to give cetuximab or panitumumab. The choice is difficult and I would say that there is probably, at this moment because we do not have the results of the direct comparison of bevacizumab and cetuximab or bevacizumab versus panitumumab, we have no specific tools to select patients for one treatment or another one. At this moment, we consider… I think it’s a little bit more fulfilling and a discussion with the patient in terms of toxicity, that a clear choice in terms of scientific data or evidence based medicine.

Are there any other data at this meeting that you think could have an impact on clinical practice?

No, I would say no. We are going more and more into the details of the selection of patients with some biological markers. There are new tools in terms of imaging techniques, we have seen this morning an interesting presentation of INOMAN working on the decrease of volume of metastases and it seems to be a little bit more precise than we have done with standard criteria such this criteria or WHO criteria. Another quite interesting thing was also the presentation of new data concerning panitumumab too, this morning.