Current Melanoma Treatments: Where Do We Stand?

SIMPLE SUMMARY: In this manuscript, we discuss recent updates on melanoma-related clinical trial data. We explore diverse topics, including new therapeutic agents and novel combinations that are being tested in early-phase clinical trials. Furthermore, we review long-term efficacy and safety data from the clinical trials that led to the currently approved drugs in the melanoma landscape. We analyze data from human clinical trials in the metastatic setting, adjuvant setting and neoadjuvant setting. Moreover, we review recent breakthroughs related to the management after resistance, as well as the discovery of new targets. Lastly, we explore clinical trials for non-cutaneous melanoma, such as uveal and mucosal melanoma. ABSTRACT: Groundbreaking research in immunology and cancer biology in the last few decades has led to the discovery and development of novel therapeutics, such as immune checkpoint inhibitors and targeted therapies, which have revolutionized the clinical care of patients with metastatic melanoma. Updated data from the largest clinical trials continue to support the use of these treatment modalities, both in the metastatic and in adjuvant settings, with studies showing the predicted plateau effect on survival curves. However, with growing evidence that neoadjuvant therapy is also associated with high rates of recurrence-free survival, the question about whether patients should receive adjuvant or neoadjuvant treatment raises new questions about therapeutic options. Finally, management after resistance and intervention with novel immunotherapies are newer challenges, particularly in the field of non-cutaneous melanoma.