Systemic Therapy for Metastatic Uveal Melanoma

Metastatic uveal melanoma (UM) is a notoriously difficult to treat malignancy with limited therapeutic options. While the ability to identify patients at high risk of recurrence based on gene-expression profiling has allowed those patients to undergo more frequent surveillance, the lack of effective adjuvant therapies has not prevented recurrences, and earlier identification of metastases has not translated into higher response rates. Chemotherapy has had very limited efficacy, even when delivered intrahepatically. Immunotherapy and targeted agents, which have revolutionized the care of patients with metastatic cutaneous melanoma, have had limited and disappointing success in UM. This chapter will discuss some of the data on various agents in the treatment of patients with advanced disease, outline some of the resistance mechanisms at play, and outline some possible attractive approaches in the future.