Adjuvant Dabrafenib/Trametinib for BRAF+ Melanoma - Episode 1
Reinhard Dummer, MD: Resected stage 3 metastatic melanoma patients have a very high risk of recurrence, and this risk is most significant in the first years after the resection. So, therefore, we recommend regular imaging in these patients, which includes ultrasound or even PET/CT scans, in order to detect the metastases quite early. Some physicians like to use irradiation therapy after resection, even if the lesions are completely resected. And in the adjuvant setting, there are several medications around. First are interferons. Second is ipilimumab, a checkpoint inhibitor that is well established in metastatic disease. However, we have to state that these treatment options really cause significant adverse events, and for ipilimumab, it’s even reported that we have 1% risk for death. So, we really have to consider this very carefully.
With the new data that we have seen during ESMO here in Madrid, the landscape changes completely. For BRAF-mutated patients, we will now have a combination of a BRAF and a MEK inhibitor, dabrafenib/trametinib. And this combination has shown very convincing data. The COMBI-AD study that investigated these 2 in the adjuvant setting was positive for relapse-free survival, overall survival, and distant metastasis-free survival. The toxicity is acceptable. So, we see pyrexia. We see adverse events that are known to be associated. However, I think they are all manageable. So, with this, we will have a very attractive treatment option for patients in stage 3 after complete resection.
The COMBI-AD study was designed for patients in stage 3 who have been completely resected. We have different stage 3s included, like 3A, 3B, and 3C. The patients were randomized to placebo-control and to an active arm. The active arm included the use of dabrafenib and trametinib. The results were very convincing. We see significant improved relapse-free survival, which is the primary endpoint with a hazard ratio below 0.5. This shows a very clear improvement for this parameter. This also translates in improved distant metastasis-free survival, and there is a clear improvement of overall survival. So, we have now a well-documented treatment option. If you compare this with treatments that are available today, such as interferons or adjuvant ipilimumab, we have to say that this is, by far, more attractive than the treatment options that I have mentioned just before.
Transcript Edited for Clarity