Evolving systemic targeted therapy strategies in uveal melanoma and implications for ophthalmic management: a review

Abstract

Uveal melanoma (UM) is the most common primary ocular tumour in adults. Despite good local control of the primary tumour with current methods, survival after the development of metastasis has remained poor over the last 30 years. After cutaneous melanoma, UM is the most common type of melanoma, and an ongoing debate exists regarding whether these conditions should be considered separate entities, particularly in the context of targeted therapy, where many of the initial trials for patients with metatatic cutaneous melanoma excluded metastatic UM. This paper will review the recent and ongoing investigations designed to validate systemic targeted therapy and immunotherapy in patients with metastatic UM and suggests ways in which these developments may affect management of UM by ophthalmologists in the near future.

Intraocular biopsy of uveal melanoma Risk assessment and identification of genetic prognostic markers

“…The most promising approach to improve survival in high‐risk patients with uveal melanoma could therefore be adjuvant therapy at time of primary treatment. Currently, no effective adjuvant agents have been identified for uveal melanoma, but several approaches are tested in randomized clinical trials (Goh & Layton ). The identification of four distinct molecular classes with different driver mutations ( BAP1 versus SF3B1 ) suggest that diverse targeted treatments are needed (Robertson et al.…”

“…). Multicentre efforts of genetic profiling have identified genes highly specific for uveal melanoma tumorigenesis and led to several potential targeted therapy strategies (Goh & Layton ). Personalized targeted treatment options hold great promise and will hopefully improve the survival of future patients with uveal melanoma.…”

The biology of uveal melanoma

“…At present, ClinicalTrials.gov lists 69 trials for metastatic UM (for recent reviews, see [65, 66]). Targeted therapies based on the activation of the mitogen-activated protein (MAP) kinase pathway by mutated G protein GNAQ or GNA11 have been tested in several clinical trials.…”

Presence and prevalence of UV related genetic mutations in uveal melanoma: similarities with cutaneous melanoma

“…Both have high progression rates to metastatic melanoma, which once detected have an extremely poor prognosis and are essentially resistant to standard chemotherapy [2]. As such, there is a significant demand for effective systemic therapies for both these malignancies, with numerous clinical trials currently underway, however many of these trials exclude UM as it is considered to have too many biological differences to CM [1,3]. Arguably, one of the most significant of these differences is the etiological involvement of ultraviolet (UV) light.…”