Treatment options for eye melanoma: a review

The authors reviewed the biology as well as current and future treatment options for eye melanoma. 

Uveal melanoma is a rare cancer (melanoma) of the eye. It involves three parts of the eye (iris, ciliary body and choroid) known together as the uvea. Eye melanoma is associated with a high risk of metastasis (spreading of cancer from the original site to other parts of the body). Almost 50% of eye melanoma patients can develop metastasis. No ideal systemic therapy (treatment that reaches cells throughout the body) for advanced uveal melanoma has been reported so far.

A better understanding of the biology of uveal melanoma is needed to develop effective treatment options. 

The authors aimed to review the biology and treatment options available for uveal melanoma.

Biology of uveal melanoma:

Studies have shown that a gene called BRCA1-associated protein 1 (BAP1 – important protein involved in cell signaling) is mutated (permanently changed) in 47% of primary uveal melanoma. The presence of this mutation also increases the risk of metastasis. Two other genes are also found to be mutated in uveal melanoma. These are the SF3B1 and EIF1AX genes. Mutations in these genes are associated with a lower risk of metastasis. Other studies have indicated that metastasis is associated with changes in activity of cells that defend the body in an immune response (effector and regulatory cells).

Treatments for uveal melanoma:

There are several studies on the role of ipilimumab (Yervoy) in the treatment of uveal melanoma. Ipilimumab is an immunotherapy, which uses the body’s own immune system to fight cancer. Uveal melanoma patients treated with ipilimumab had a response rate of 5%. Patients had a  3 month disease control rate of 36%. Patients who had more than 1000 immune cells per µl had an overall survival (patients who were still alive following treatment) of 13.4 months. This was compared to 4.8 months in patients who had less than 1000 immune cells per µl. Based on the studies analyzed, patients received the maximum benefit from ipilimumab treatment if they were treated earlier in their disease and if their immune systems were not compromised.

Based on recent findings, targeted therapy (drugs targeting a specific gene or protein) could be an effective treatment for uveal melanoma. Selumetinib (AZD6244) is one such targeted therapy which blocks the functions of proteins known as MEK 1 or 2 (important proteins in cell signaling). Based on study results, progression-free survival (time following treatment before the disease progressed) in patients treated with selumetinib was double that of chemotherapy.

Clinical trials:

As of 2014, several clinical trials for uveal melanoma were on going. These were: a phase I/II clinical trial involving a dendritic cell vaccine (vaccine made from patients’ own immune cells) and a phase II trial of sunitinib (Sutent, – targeted therapy) in combination with chemotherapy drugs tamoxifen (Nolvadex), and cisplatin (Platinol).

The authors concluded that targeted therapy would be more effective in treating uveal melanoma. They further suggested that patients should be referred to specialized centers for fast and appropriate treatment for this rare disease.