Systemic treatment of metastatic uveal melanoma: review of literature and future perspectives

Kristina Buder, Anja Gesierich, Götz Gelbrich, Matthias Goebeler, Kristina Buder, Anja Gesierich, Götz Gelbrich, Matthias Goebeler

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.

Keywords: Clinical trials; drug therapy; metastatic; review; uveal melanoma.

© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Flow of information through the different phases of the review process according to PRISMA statement .
Figure 2
Figure 2
Response rates for single-agent chemotherapies (A), combination chemotherapies (B), and chemoimmunotherapies and immunotherapy with ipilimumab (C).
Figure 3
Figure 3
Response rates for agents with antiangiogenetic effect (A), kinase inhibitors (B), and comparison of all treatment modalities (C).

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