ASCO 2015

Cobimetinib plus vemurafenib for advanced BRAF-mutated melanoma

Dr James Larkin - Royal Marsden Hospital, London, UK

You are presenting here on cobimetinib, MEK inhibitor, and vemurafenib, BRAF inhibitor, in melanoma. What setting and how is that comparable to what we’ve been hearing about checkpoint inhibition?

What I presented here was an updated analysis of the coBRIM study. It was initially published and presented at ESMO in Madrid in autumn last year and it came out in the New England Journal of Medicine. What I presented was an updated analysis for progression free survival. In the updated analysis what we saw actually was that the median progression free survival in the combination arm, so that’s vemurafenib and cobimetinib, was just in excess of 12 months which is the first time we’ve actually seen it just in excess of 12 months in melanoma.

And how do you square these sorts of findings with totally different mechanisms with the other very interesting results we’ve been hearing on checkpoint inhibition here at ASCO?

Yes, I would see that the two classes of drug, targeted therapy and immunotherapies, as being complementary. What we have here is in the last few years in melanoma, the last five years, we’ve seen a lot of progress with targeted therapy; we’re seeing progress with immunotherapy at the same time. I always say this isn’t a competition, we have a situation with our patients where we actually have two big breakthroughs and what we need to do is to use these drugs in the best way for our patients to extend their lives as long as possible and maintain their quality of life.

How do you think they’re going to impact practice then, practically, for cancer doctors?

I think they already are beginning to impact practice. We already have approved BRAF inhibitors, we have ipi which is an immune checkpoint inhibitor and the next generation of the PD1 drugs and we’re beginning to see results from the PD1 drugs. We’re seeing combinations of PD1, so nivolumab, in combination with ipilimumab and we’re seeing combinations of BRAF plus MEK. So that’s where we are now.

So how big a slice of the cake do you think cobimetinib and vemurafenib are going to take?

40% of patients with melanoma will have BRAF mutations or thereabouts and so what that means is that most of those patients with BRAF mutant melanoma will be treated with BRAF targeted therapy at some time during, if you like, the course of the disease.

So if you’ve got MEK targeting, BRAF targeting can you add checkpoint inhibition as well?

To that, well again that would be something that would need to be studied properly in clinical trials. I actually think that combinations of drugs beyond two is probably challenging, actually, in lots of different ways. I think it’s more of a priority to understand rationally what we’re doing already and, frankly, why would you need to give two drugs if you could give one drug.

Now what, then, do you advise doctors to take home from your findings from this very interesting coBRIM study?

Yes, I think the take home message for the update on coBRIM is that the initial efficacy signal that we saw has been maintained in terms of progression free survival. I guess perhaps the headline is that the median progression free survival on vemurafenib and cobimetinib was just in excess of 12 months, in comparison with 7 months for vemurafenib. So that’s definitely a clinically and statistically relevant result.