AACR 2014

Impact of the liver environment upon the efficacy of induction therapy

Dr Frederic Bibeau - Institut regional du Cancer, Montpellier, France

Can you tell us more about your work surrounding environmental circumstances of the liver?

We looked at the impact of induction treatment in patients having liver metastases and we tried to see if there was any difference between surgically resected patients versus patients having systemic treatment and targeted therapies to have a regression of liver mets. What we found was that there was immune response and changes in the microenvironment after induction treatment.

So is this the use of neoadjuvant therapy to make surgery possible?

This was not the main question because we know that induction treatment, neoadjuvant treatment, makes surgery possible for patients having liver mets that are not initially resectable. What we looked at was the consequence of this regression after induction treatment and one of the consequences was, besides tumour regression, the enhancement of an immune response after induction treatment.

Can you tell us what you did with these three treatments?

In fact we didn’t use three different treatments, we only looked at liver metastases in the induction treatment strategy. This strategy can be based on chemo, chemo with targeted therapies such as cetuximab, an anti-EGFR antibody, and bevacizumab, an anti-VEGF antibody. We tried to compare the effect of induction treatment with surgery resected patients and surgery resected patients with this treatment.

Did it make a difference whether you combined anti-EGFR with chemo, anti-VEGF with chemo or used chemo alone?

We didn’t see any difference except for anti-EGFR antibody with a stronger immune response with CD45 T-memory cells. So I may be careful because this was only small groups, making the comparison difficult. But what the evidence was a strong difference between patients having surgery alone versus patients having surgery after induction treatment.

So there was an immune consequence for using systemic therapy?

In fact, having chemotherapy or having chemotherapy with targeted therapy induced an immune response and changes within the microenvironment of liver mets. So the question is is the cause or the consequence of tumour regression? This is a difficult point to answer but we will try to find the answer with further work.

Should this give hope to patients with liver metastases?

It’s too early to give a definitive response but we know that the immune response within the field of oncology is getting more and more important. So working in a metastatic setting and in liver mets and having … to the tumour and to the microenvironment, to the host, is a very important hope for patients. We know that targeted treatments and immunomodulation have led to good results in some solid tumours such as melanoma. We would hope that there will be an overlap in the metastatic setting with patients having liver mets. But I would say that it’s a little bit too early to introduce this kind of treatment in this setting.

What should oncologists take from this?

I think they should pay attention to this, to the host, and they should be aware of clinical trials in digestive oncology using targeted treatments within the field of immunology.