I am at a patient and physician meeting the MRF is hosting and hearing data from some excellent melanoma doctors. A couple of things have stood out so far:
We have seen data that for patients whose tumor has the BRAF mutation, combinging a BRAF inhibitor plus a MEK inhibitor is better than the BRAF inhibitor alone. We also know that most patients respond to these drugs for a few months then the tumor finds away to work around these inhibitors. The question remains whether you should take a BRAF inhibitor first and save the combination for after the BRAF alone stops working. Data now shows that people who have progressed on BRAF monotherapy do not perform as well on the combination as do people who have not had prior BRAF therapy. This suggests it is better to start with the combination.
About 50% of melanomas have the BRAF mutation. Another 20% have an NRAS mutation. Data now suggests that patients with an NRAS mutation respond better to the immunotherapy drug ipilimumab (Yervoy). This may be because NRAS patients tend to be older and more tied to long-term UV exposure, and older patients tend to have more mutations in their tumors overall. This, in turn, may make those tumors easier targets for the immune system once it becomes activiated against tumor cells.