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.Forty clinical studies on metastatic uveal melanoma were reviewed regarding responses to systemic treatments. New insights into genetic and molecular background led to investigation of new substances but promising in vitro data have not yet been translated into satisfying treatment responses; however, preliminary results of ongoing studies are highly encouraging.

Reduction of Nodular Growth Pattern of Metastatic Uveal Melanoma after Radioembolization of Hepatic Metastases

“…Although to date systemic chemotherapies for metastatic uveal melanoma have been relatively unsuccessful [5], a variety of new treatment approaches are currently under exploration. Recent investigations of targeted molecular therapies including BRAF and MEK inhibitors appear to demonstrate a survival or progression-free survival benefit among patients with metastatic melanoma harboring certain genetic mutations [13,14,15].…”

“…With no effective systemic chemotherapy available [5], embolization is an important locoregional method of palliation for metastatic disease [6]. Herein, we report a case of worsening hepatic sinusoidal infiltrative metastatic uveal melanoma in the setting of regressing radioembolized nodular liver metastases.…”

High Doses of Ascorbate (Vitamin C): A New Frontier in the Treatment of Intraocular Cancer

“…However, as previously mentioned, up to 50% of patients develop metastatic disease, with spread of tumour cells to liver (89%), lung (29%), bone (17%), and other organs [104,105], and this event represents a clear indication to systemic chemotherapy. Unfortunately, although various chemotherapeutic agents have been tested so far, like dacarbazine, fotemustine, or gemcitabine/treosulfan, the impact of systemic chemotherapy on patients' survival is questionable [106,107].…”

A phase 2 study of tremelimumab in patients with advanced uveal melanoma

“…Almost half of all cases will develop metastatic disease, with a median survival ranging from 3.6 to 19 months and a 1-year overall mortality of 80% [2][3][4]. Despite advances in local management and the discovery of prognostic biomarkers, there is currently no standard treatment for advanced cases of this melanoma subtype [5][6][7].…”