EADO Congress 2015

Prognostic value of BRAFV600 mutations in stage 3 cutaneous melanoma patients

Prof Philippe Saiag - University of Versailles, Versailles, France

You’ve been looking at the prognostic value of BRAFV600 mutations and this is in melanoma, what were you looking at? What kind of melanoma and why were you looking at this?

We were looking at the prognostic value in stage 3 melanoma patients, the stage 3 melanoma patients as the patients with lymph node involvement or in transit mets, and the prognosis of such patients is very unprecise, it ranges from 20-25% at five years to 87% at five years alive. So it has to be refined and the thing that was important for us to do the job is that is we now have drugs that are active on BRAF mutated melanoma and there are trials that have been done and we are waiting for the results on dual inhibition as an adjuvant therapy. But we were not able to know what is the exact prognosis of those patients at stage 3 according to their BRAF status or not. So we did a validation study because we did a small retrospective study which was published in the Archives of Surgical Oncology in 2012 which showed that the presence of a BRAF mutation was associated with a worse prognosis with a hazard ratio of 2 for distant metastasis, for survival and overall survival. We used a cohort, a prospective cohort, of patients which recorded a lot of patients and we looked at all stage 3 patients and we took their tumours and their metastases in the lymph nodes, and looked and assessed their BRAF status and then looked at the outcomes. Then at the end we made a multivariable analysis and what came first the AJCC staging, the age and the BRAF status. These three factors are the three main prognostic factors involved in stage 3 melanoma.

So BRAF status, mutated BRAFV600, is negative it gives you a higher risk but on the other hand…

If it is mutated it gives you a high risk with a hazard ratio of nearly 2.

And you can target it, though, so how does that change the clinical picture for doctors now and in the future looking ahead?

Today I think not, it will not change, but within one year, one year and a half, we are going to have the results of the trials that have tested the BRAF inhibitors plus MEK inhibitors in that situation. I think they will be positive so we have to give the advice to the patient should I take this drug or not because it’s one year of treatment, it’s a costly treatment. So it’s very important to give to the patient their prognosis in terms of a chance of relapse and chance of death at five years in order for the patient to make their choice. Because when you are at adjuvant treatment, it’s different. All the patients are not going to die and some patients don’t want to be burdened with the disease, others are very anxious and they want everything to be… So it’s important to have the exact prognosis. And I gave you the figures of the stage 3 and it is such a huge variation between so we have to be more precise. If you have a stage 3c BRAF mutated melanoma and you are more than 50 years of age the prognosis is very, very bad so you should take the treatment.

So you’re getting some information to help you individualise therapy, what is the overall clinical picture, then, emerging from this, if you could summarise that for cancer doctors?

For cancer doctors, I think the cancer doctors should have the patient tested for melanoma, for BRAF testing, for stage 4 of course, because it leads to the targeted therapies, but also at stage 3 because you have better insight into the prognosis and you have also the results ready in case they become stage 4.