EADO Congress 2015
New drugs and new trials in melanoma
Prof Jean-Jacques Grob - Marseille University, Marseille, France
You’ve been pulling together details of clinical findings on ipilimumab and nivolumab. Tell me what it is you were doing. I want to get some kind of feel of where we are with these two drugs now.
We are starting to understand how to combine different immunotherapies and the two ones which have been developed are so far anti-PD1 and anti-CTLA-4. So first was to combine them together at the same time and now we’re trying to sequence them in a different order. So the results are preliminary but basically what we understand from the trials available now and from the partial data that we have, because these trials have been started not so long ago, that a combination of anti-CTLA-4 and anti-PD1, namely ipilimumab and nivolumab, you obtain a much better PFS than with ipi alone. But it’s now difficult to know exactly whether the combination of ipilimumab and nivolumab is much better than nivolumab alone. This question will be hard to answer with current trials because the trials have not been designed statistically for that.
But the PD-L1 marker comes into this, doesn’t it?
Yes. It was more or less expected that in fact ipilimumab would be more useful in patients with not a high level of expression of anti-PD-L1 at the level of the tumour. This is what is observed. So the benefit added by ipilimumab to nivolumab seems to be limited to this population. But this is a rather fragile result for the moment and we all know that the expression of PD-L1 on the tumours is highly variable, depending on the sample that you are taking, on the techniques that you are using and on the threshold for this technique. So the results are not that strong so far.
Provisionally, then, using nivolumab first, or the PD-1 agent first, seems to be right or definitely using that but you could add the CTLA-4 agent too?
We probably, on what we can say right now and it’s changing very rapidly, as you know, the basics should be to start with anti-PD1 except probably in a subgroup of population which we have to define and which could be defined by the expression of PD-L1 or maybe by the fact that they have more active disease with an immediate danger for the patient so that you could say that you will have one shot but not two.
So could you summarise where we are in terms of responses and long-term survival with these drugs?
At the moment we don’t have long-term survival, not at all. We have the first results on PFS and what we see is a different hazard ratio but we have to see now the overall survival and this will be for the next meeting.
And what can we say about adding in other therapies beyond immunotherapy?
It’s too early to answer this question. The problem is now that we have different treatments which are efficacious, so BRAF and MEK inhibitors on the one side, immunotherapy with two different molecules, anti-PD1 and anti-CTLA-4, and of course other molecules are already available with different targets. But already at that point it’s difficult to know which should be the first treatment in which patient, when, and then if there a sequence which one should we start first and what will happen next. This will be discussed in the next steps of the meetings.
Right, so what’s the very brief take-home message for doctors coming out of your talk about these combinations of immune checkpoint inhibitors?
Very promising in terms of results, highly toxic and only manageable if you have got a very trained team. Then you have to dedicate probably the strategy to a subgroup of patients which is not so far well defined.
