OBJECTIVES : Uveal melanoma (UM) is a rare eye cancer that represents a major challenge for physicians: 50% of patients go on to develop metastases, 95% of which are localised to the liver (Kujala et al. 2003, Yang et al. 2018). The median survival time is 6–12 months after a distant metastasis has been detected (Nathan et al. 2015). We have performed a systematic literature review (SLR) to identify the clinical evidence for systemic and targeted treatment interventions for metastatic UM (mUM).

METHODS : Search strategies were developed to recover publications reporting clinical data for adult patients with mUM. Studies meeting the inclusion criteria were identified and key data were extracted. Reported outcomes of interest were overall survival (OS), progression-free survival (PFS), disease control rate, safety and quality of life. The methodology followed international guidelines, and records were independently reviewed by two analysts and quality-assessed.

RESULTS : The searches identified 1,341 records; 55 matched the inclusion criteria of the review, 12 were RCTs and 43 were single-arm trials. These studies collectively presented clinical outcomes for 53 systemic treatment arms and 12 localised treatment arms, with a range of patient numbers (n=5–120; median 23). Systemic interventions included chemotherapies, targeted therapies, and immunotherapies. Localised treatments included the liver-directed therapies (LDT), chemotherapy delivered by hepatic perfusion, immune-embolism, and radio-embolism. Studies on LDTs generally reported longer OS compared to systemic therapies. There was no clear difference in the maximum PFS time between LDTs and systemic therapies. Across all studies there were 1,511 patients evaluable for response, five (<0.3%) achieved a complete response and 119 (8%) achieved a partial response.

CONCLUSIONS : The clinical evidence for effective treatments for mUM remains limited. Response to treatments is very low, prognosis is poor, and survival rates have not significantly improved in the last 40 years.