BRAF and MEK inhibitors in the era of immunotherapy in melanoma patients

The treatment landscape in advanced melanoma is changing dramatically with the approval of new drugs. Vemurafenib was the first approved targeted agent for the treatment of BRAF-mutant advanced melanoma. However, treatment with a BRAF inhibitor is linked with acquired resistance occurring in half of the patients after approximately six months. Combination of MEK and BRAF inhibitor therapy results in extension of the time to resistance, translating into longer overall survival of treated patients. Similar clinical benefits are observed with therapy using antibodies against immune-checkpoint inhibitors in the same patient population. Due to the fact that results of randomised studies comparing these two treatment strategies back to back have not been presented yet, the best first and second line treatment option in patients with BRAF-mutant melanoma is unknown. Currently, phase 3 studies are also evaluating the efficacy of targeted therapy combined with immunotherapy in patients with BRAF-mutant and BRAF wild-type advanced melanoma. Identifying a biomarker for the selection of patients benefiting most from the treatment will be crucial for further survival improvement in patients with advanced melanoma.