This is an historic clinical trial because ipilimumab was the first drug in metastatic melanoma, an immunotherapy drug, to show survival advantage in randomised trials. We now know that one in four patients with widespread metastatic melanoma will have long-term survival with ipilimumab. So this was the first study to bring ipilimumab into the high risk, surgically resected stage 3 melanoma and the ERTC compared ipilimumab to placebo.

The importance of bringing it to that group of patients is what?

Is that they have a very high risk of recurrence. These patients with high risk stage 3 disease may have anywhere from a 50-75% risk of recurring and dying of their melanoma despite the fact that it has been surgically resected. This drug, compared to a placebo, delayed the recurrence by, on average, about 9 months and at 3 years there was approximately a 10% difference in relapse rate between a placebo and ipilimumab. Now that is not unlike, or it is comparable to, the drug that is already on the market, interferon, which is approved by the FDA for high risk stage 3 melanoma. So what we didn’t see today is any survival benefit, it’s too early for the study to have that. We did see some pretty considerable toxicity, including patient deaths; there were five patient deaths directly attributable to the drug. So whereas I think it’s certainly a step forward in proof that these checkpoint inhibitors not only work in metastatic but have activity, meaning they’re delaying recurrence, it’s still modest at best and the toxicity profile is significant and we need larger follow-up studies, survival on this study, before we make any final decisions about when we should use that.

Does this mean that some of the studies we heard about with ipilimumab recently showing plateaus in survival were by very carefully selected patients?

No, in metastatic melanoma it’s very clear that approximately 25% of patients who get ipilimumab have long-term plateaued survival. I think the question is since you can rescue, basically, one in four patients with these drugs in the metastatic setting, the question is can you rescue more, meaning cure more of them, in the adjuvant setting. Now, today’s data did not talk about survival, it just talked about delaying recurrence which in melanoma has not always correlated with improved survival. We need to wait for that data given the toxicity profile. In the US there is a large inter-group study that’s finishing comparing ipilimumab to the standard in the United States, which is high dose interferon, directly; this study compared it to placebo.

So what do doctors or should doctors take home from this study today?

I don’t think this is a practice pattern changing therapy at this point in time. I think it’s promising, it’s exciting but I think we need to wait for both survival data from this trial as well as the direct interferon versus ipilimumab US trial and put the toxicity in context before we make general recommendations in the US.