Melanomas harboring an activating BRAFV600 mutation account for 50% of all advanced melanomas. The approval of BRAF-targeted therapy revolutionized treatment of these patients with achievement of impressive responses. However, development of resistance to these drugs is a significant problem, and as such, duration of response remains low, with median progression free survival of around 11-15 months. Immune checkpoint blockers exploit the immune system to eradicate cancer and can produce durable disease control that results in long-term, treatment-free survival in some patients. These drugs have shown very impressive survival in patients with BRAF-mutated melanoma. Thus, there is a need to continue to utilize emerging data to achieve long-term disease control for patients with advanced melanoma. Combining targeted therapy with immune therapy may be one possible way to achieve this goal. In this review, the mechanisms of action of these two pathways, including the mechanistic basis of this combination, are summarized, along with results of completed and ongoing trials in triple therapy.
Keywords: BRAF mutation; checkpoint inhibitor; combination immunotherapy; melanoma; targeted therapy.
© The Author(s), 2022.