This is a randomised phase II study where the patients were randomised to receive the combination of nivolumab plus ipilimumab versus ipilimumab in a 2:1 randomisation.

What we found is that the patients who received the combination, and with a focus on the BRAF wild-type population, had a 61% response rate and all patients who received the combination had a 22% complete response rate.

You also got a response in BRAF mutated, didn’t you?

Yes, in both.

The complete response rate just happened to be the same in both BRAF mutated and BRAF wild-type patients.

What are the data coming out of this? You’ve got quite an impressive hazard ratio, haven’t you, and overall response rates are very, very promising.

Yes, the hazard ratio when we were looking at the progression free survival in favour of the combination was 0.4 with a significant p-value.

Clearly this combination is not licensed yet but do you think it should be very soon?

Given the activity, the response rate, the complete response rate, I would say cautious with some of the side effects that were manageable but did require intervention with the means of steroids.

I think that this should be something that is considered in an armamentarium for patients up front, first line for the treatment of metastatic melanoma.

This was two checkpoint inhibitors, is it the right two to be combining? Are there others, other possibilities?

These are the two that have been most advanced clinically and most developed clinically so these make the logical ones.

There are other ones that are now coming out in more phase I early studies and how we combine immuno agents together, either being checkpoints or other aspects, how we combine with targeted therapies, how we combine with chemotherapy or radiation etc., is really an evolving clinical science that will need more investigation and more maturity of the data.

What is your recommendation presently to cancer doctors about the way this is going and what are the likely therapies for melanoma in the very near future?

We now have anti-CTLA4 and anti-PD1; right now, at least, in terms of our ability the anti-PD1s are after ipilimumab in terms of how they have been approved.

There is data that has come out in terms of its drug comparison in the front line setting and now with our data here showing the combination in the front line setting.

So the maturity of the data for follow-up for survival, for looking at the phase III trial that has been completed combining nivolumab plus ipilimumab versus nivolumab alone versus ipilimumab alone in a three arm study, whilst it will give us further insights into data and how to guide such recommendations.

So the good news – we have many novel agents now recently approved and some combinations in the future that we have to offer to our patients.

Is it your belief that combinations of checkpoint inhibitors trump using them sequentially?

That is something that needs to be further investigated.

We do have sequential trials that have looked at giving one first versus the other and vice versa.

Those data need to mature but having in combinations at the same time a high response rate with a complete response rate is something that is hard to ignore and will obviously need further follow-up in maturity.

Finally, could you give a very brief take home message for cancer doctors, busy cancer doctors? What is that right now in terms of melanoma and what to do about it?

Right now, looking at two checkpoints together in combination it does have high response rates, it does have a significant complete response rate but toxicity must be monitored and managed well.

This is another part of the armamentarium that we can consider for patients with metastatic melanoma possibly in the future to treat this disease.