Combining immune-based therapies with TKIs in melanomas

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Published: 4 Jul 2017
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Prof Caroline Robert - Institute Gustave Roussy, Paris, France

Prof Robert speaks with ecancer at WIN 2017 about tackling class-associated toxicity and drug resistance with combination therapies based on tyrosine kinase inhibition.

Intralesional oncolytic therapies for melanoma were also discussed by Dr Sanjiv Agarwala at EADO 2017, here. 

I just made the point today about where we are with these treatments. We have improved immensely the field by using either targeted therapy for patients with BRAF mutant melanoma, which concerns about half of our patients, or immunotherapy with checkpoint inhibitors, initially ipilimumab blocking CTLA-4 and then nivolumab or pembrolizumab blocking PD-1. Now we already are at the second generation of these two strategies. I mean that for targeted agents the first generation with BRAF monotherapy and now we use BRAF and MEK combined and for immunotherapy we had ipilimumab and now we have anti-PD-1 and now we begin to combine ipilimumab and anti-PD-1. So we have improved and then further improved.

And now the question, and that was the subject of this talk, was how and is it going to be interesting to combine these two approaches? Because of course when you have two treatments that work with different mechanisms that give good results you would like to combine them. So we have a toxicity issue that we have to take into account but we already have some preclinical data that seems to say that it would be interesting to combine and we also have some ideas that in some instances it might be also a smart thing to combine, meaning not to give all together at the same time but to give one approach, one strategy, and then to use another one either when the patient develops resistance or even sometimes maybe before the resistance is occurring. So that’s what we are exploring with clinical trials right now and we don’t really have answers. We have big phase III of combinations that enrolled presently our patients and we also have sequencing trials and the response is going to happen in a few years.

Are there any combinations that include oncolytic virus therapy or intralesional injections for the melanoma?

I was mostly asked to talk about targeted agents but we also have a combination with an intratumour injection of oncolytic virus, like the TVEC. It’s combining with pembrolizumab and it seems to be interesting.