Controlling brain metastases, it was very interesting because definitively now we know that the combined therapy with anti-PD-1 and ipilimumab, I mean immunotherapy, is the best treatment for brain metastases. Question: is it to use alone or with radio-stereotactics in the future? In the next year we will have the answer. But definitively even if you have a patient which is BRAF positive we are now discussing to use this combination first.

Is toxicity a risk with this treatment?

Concerning the toxicity of immunotherapy, clearly we have more and more toxicity but what we know is that it starts early but it disappears after. So we have many different continuous manifestations, so often it could be a problem of diagnosis. When you have severe, grade 3 or 4, adverse events we know that it could be a link with the clinical response.

Would adding radiotherapy increase the risk or does that remain to be seen in the data?

We don’t know, we don’t have still the answer about that but probably in one or two years, yes, because clinical trials are ongoing.

When it comes to the new wave of immunotherapies, are they offering any different actions or insights?

At the moment, really we are more in the combination. I mean that, by example anti-PD-L1, we don’t use it alone for melanoma but we are combining anti-PD-L1, anti-PD-1 and ipilimumab. You are more in this kind of approach. It means that we know today that we have around 50% of response with the combination and even in some situations 60-70%, I mean with ipilimumab and anti-PD-1. So now it means that we would like to increase so far the 30 other percent of patients not responding to treatment. It’s why we try either to combine targeted therapy with immunotherapy or immunotherapy with another third monoclonal antibody.

Is that for any particular patient subgroup?

Definitely in melanoma it does not work, it means that you can have 1%, 5%. We tried different things, it’s not a good marker for clinical response for immunotherapy. It’s completely different in other types of cancer.

Are there any biomarkers for the combined therapy?

We have mainly the TIL which is very important, that is the infiltration by T-lymphocytes. For me, it’s probably one of the best markers that we have today.

What are the take home lessons?

Now we can already say if you have brain metastases now we have a treatment with immunotherapy. Minimum anti-PD-1 and if you can use it the combination is even better because from 20% of clinical response you could increase ? with ipilimumab 40% of clinical response. Probably it will be interesting to make the association between immunotherapy and radiotherapy so we know that we don’t increase the adverse events but the question is to have exactly the same tools, the same machine for radiotherapy and that is the main problem today and also according to the profile of the radiotherapist. So it means that here we have a variable that we have to manage.