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Modern combined targeted and immunotherapy of metastatic skin melanoma

Melanoma of the skin is one of the most aggressive malignant neoplasms. Metastatic skin melanoma has an extremely poor clinical prognosis with a high mortality rate, accounting for 80% of all deaths from skin malignancies. The approaches to the treatment of metastatic skin melanoma have been dynamically developing over the past decade. New drugs and their combinations are becoming more affordable. In connection with the advances in molecular genetics and the development of new targeted drugs, treatment outcomes have significantly improved: first of all, overall survival and the time to progression of the disease, which has set new challenges for continuing research in this area. The development of new treatment options for patients with inoperable and/or metastatic melanoma with a mutation in the BRAFV600 gene is still in high demand. Emerging data from clinical and preclinical studies suggest that synergies can be observed between inhibitors of immune checkpoints and inhibitors of BRAF and MEK. Despite the fact that inhibitors of the BRAF signaling pathway have a high frequency of objective responses, in most cases their duration is short. Inhibitors of immune checkpoints provide a longer lasting effect, but the response rate is relatively low. Combining the two types of therapy can improve survival rates over the long term. This review demonstrates the results of phase III randomized trials that have allowed to determine the current standards in the treatment of metastatic skin melanoma. We also demonstrated our own experience of using a triple combination of targeted therapy with BRAF/MEK inhibitors in combination with PD-1 inhibitors.