The role of targeted therapy for melanoma in the immunotherapy era

Over the past 10 years of remarkable development of both molecularly targeted and immune-targeted therapy for the treatment of melanoma, a clear preference of immunotherapy over molecularly targeted therapy has emerged among melanoma treatment providers. Still, the clinical data remain remarkable for patients with BRAF-mutant stage III and IV melanoma, and there seems to be a clear benefit of BRAF-targeted therapy for these patients. The key, then, is to identify the best way to use BRAF-targeted therapy. In this review, the clinical data of molecular-targeted therapy are summarized, mechanisms of resistance to single-agent BRAF and combined BRAF with mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitor are discussed, and strategies to overcome this resistance are presented; then, we review a number of clinical dilemmas that influence the decision-making of using targeted therapy over immunotherapy, and viceversa, and help define the specific role of targeted therapy in the immunotherapy era.