Adjuvant Therapy in Melanoma: COMBI-AD Trial

Transcript:

Axel Hauschild, MD: So my question for Caroline is on adjuvant treatment modalities. There was an update on COMBI-AD at this year’s ESMO [European Society for Medical Oncology] conference, and the data were published on the same day. Can you summarize the findings of this clinical trial and also remind us on the design of the clinical trial?

Caroline Robert, MD, PhD: Yes, it was a randomized phase III trial with 2 arms — placebo versus dabrafenib plus trametinib.

We already have seen the results. They have been published in the New England Journal of Medicine. We know that we have a very significant benefit in terms of relapse-free survival with a ratio of 0.47. We also have the 3-year overall survival data that statistically did not really reach the prespecified points, but we all know there are very good results.

Now we have an update of this trial with a 4-year follow-up. We still have a very good relapse-free survival benefit and a very good distant metastasis-free survival benefit. The hazard ratio has changed a little bit; it’s 0.49.

We also have something quite original in our field. It’s not something that is new in the oncology field. There was a calculation done by the statistician of the cure-rate model. If you look into all of these papers, it’s really mathematics. It’s very difficult to understand. It’s full of questions. But there are several models that have been developed to try to predict the rate of cure. This is based, of course, on the follow-up. You cannot do that in a very young curve. If you have a lot of events very early, you cannot. So you incorporate some data on the biology of the disease. It’s different from one concept to the other. But then, at the end, it’s a quite-strong mathematic model to predict that death is not going to occur in these patients. So patients are so-called immune or cured. And based on this model, it seems that the survival curve is totally superimposed with the cure-rate model curve.

When you see that, it’s very impressive. At first, you might think that it’s strange. But in fact, it’s from calculation. In the end, it seems that with the dabrafenib-trametinib arm, 54% of patients are cured. In the placebo arm, this number is only 37%.

Jason J. Luke, MD, FACP: I wanted to follow up on that and note why I think it’s particularly important for clinical practice. When we initially saw the curve for relapse, there was quite a dramatic benefit in the first year. But we started to see that curve fall precipitously when patients were initially taken off drug. There was clear delta there at a benefit of 3 years. Then the question in the field was, what’s that going to look like over time? If it continued to drop, maybe you’re pushing it back or you’re not curing the patients. Many had already believed that there truly would be a delta there, but this kind of data is very reassuring. You are truly giving patients the potential for cure by giving them this therapy.

Caroline Robert, MD, PhD: Yes. I forgot to say, very important, that the treatment is given for 1 year. Because of what we know about targeted therapies, the fear is that the patient is going to drop at 1 year. That’s very important here.

Axel Hauschild, MD: Yes. I think it’s very important that you maintain the benefit between the difference between the 2 curves over time. This has been shown, and they are nice data. There was also a risk in the very beginning. If the curves collapse over time, after 4 or 5 years there’s no difference. But now there’s the big delta, and they are very promising data. I need to say that the quality of life of the patients, which has been evaluated, is extremely good. Twenty-five percent of the patients stepped off because of some toxicities during their 1 year of treatment. But there is exciting data.

Transcript Edited for Clarity