title: Systemic treatment of metastatic uveal melanoma: review of literature and future perspectives.
abstract: Up to 50% of patients with uveal melanoma develop metastatic disease with poor prognosis. Regional, mainly liver-directed, therapies may induce limited tumor responses but do not improve overall survival. Response rates of metastatic uveal melanoma (MUM) to systemic chemotherapy are poor. Insights into the molecular biology of MUM recently led to investigation of new drugs. In this study, to compare response rates of systemic treatment for MUM we searched Pubmed/Web of Knowledge databases and ASCO website (1980-2013) for "metastatic/uveal/melanoma" and "melanoma/eye." Forty studies (one case series, three phase I, five pilot, 22 nonrandomized, and two randomized phase II, one randomized phase III study, data of three expanded access programs, three retrospective studies) with 841 evaluable patients were included in the numeric outcome analysis. Complete or partial remissions were observed in 39/841 patients (overall response rate [ORR] 4.6%; 95% confidence intervals [CI] 3.3-6.3%), no responses were observed in 22/40 studies. Progression-free survival ranged from 1.8 to 7.2, median overall survival from 5.2 to 19.0 months as reported in 21/40 and 26/40 studies, respectively. Best responses were seen for chemoimmunotherapy (ORR 10.3%; 95% CI 4.8-18.7%) though mainly in first-line patients. Immunotherapy with ipilimumab, antiangiogenetic approaches, and kinase inhibitors have not yet proven to be superior to chemotherapy. MEK inhibitors are currently investigated in a phase II trial with promising preliminary data. Despite new insights into genetic and molecular background of MUM, satisfying systemic treatment approaches are currently lacking. Study results of innovative treatment strategies are urgently awaited.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Josef-Schneider-Strasse 2, Würzburg, 97080, Germany; Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Josef-Schneider-Strasse 6, Würzburg, 97080, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Buder
authors.forename: Anja
authors.initials: A
authors.lastname: Gesierich
authors.forename: Götz
authors.initials: G
authors.lastname: Gelbrich
authors.forename: Matthias
authors.initials: M
authors.lastname: Goebeler
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary; D016896:Treatment Outcome; D014604:Uveal Neoplasms; D000098943:Uveal Melanoma
chemical_list: D000970:Antineoplastic Agents
keywords: Clinical trials; drug therapy; metastatic; review; uveal melanoma