Identifying the optimum first-line therapy in BRAF-mutant metastatic melanoma

Introduction: The emergence of molecularly targeted agents and immune checkpoint inhibitors has positively revolutionized the management and prognosis of BRAF-mutant metastatic melanoma. However, the availability of both therapeutic options, with their pros and cons, rationally triggered clinical considerations for the optimum frontline and subsequent treatment decisions. Areas covered: Here, we debate all approved therapies in patients with BRAF-mutant metastatic melanoma evaluating their efficacy and safety based on their pivotal trials. With prospective randomized data pending, retrospective comparisons of BRAF/MEK versus immune checkpoint inhibitors are reviewed to recognize any advantage between these two alternatives and to optimize their implementation. Preclinical and early clinical results of combining concurrently or sequentially targeted therapy and immunotherapy are also discussed. Expert opinion: BRAF/MEK inhibitors produce rapid and deep responses and should be included in first-line approaches, particularly in cases with aggressive and bulky disease, while single or double checkpoint inhibition lead to more durable responses and could be involved either in frontline treatment of BRAF-mutant melanoma with less unfavorable characteristics or in maintenance after initial targeted induction or in future immune/targeted regimens for high-risk groups. Data from ongoing trials directly comparing or combining these strategies are expected to update their role in a more individualized basis.