Targeted Therapies in Combination With Immune Therapies for the Treatment of Metastatic Melanoma

Abstract In recent years, the field of oncology has witnessed many breakthroughs in the treatment of advanced malignancies, particularly in patients with advanced melanoma. Targeted and immune checkpoint therapies have emerged as the primary treatment strategies for these patients. Molecular profiling of melanoma is incorporated into routine practice to identify potential therapeutic targets, and patients are offered either a targeted or immune checkpoint inhibitor therapy approach. Both strategies have limitations where not all patients experience durable responses. Preclinical data have demonstrated the ability of targeted therapy to enhance activity of effector T cells, reduce immunosuppressive cytokine production, and increase tumor cell antigen presentation, which can augment antitumor immunity. In vivo models have shown synergy with improved tumor control when targeted and immune checkpoint agents are combined. Therefore, combination strategies with targeted and immune checkpoint therapy may improve patient outcomes. Early clinical data with anti–programmed cell-death protein 1/programmed cell-death ligand 1 agents in combination with targeted inhibitors appear to have acceptable toxicity rates and the potential for enhanced antitumor activity. This review explores the current status of preclinical and clinical development for these combination approaches in patients with advanced melanoma.