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SystemIC Treatments

Although there are currently no FDA-approved systemic treatments for metastatic uveal melanoma, some clinicians recommend treatment with therapies that have been FDA-approved for cutaneous melanoma. In addition, ongoing clinical trials may give patients access to systemic agents before they are approved. 

Immunotherapy

A type of systemic treatment given to activate a person’s immune system so that it will destroy melanoma cells within the body. Several immunotherapies are FDA-approved for cutaneous melanoma and some are being studied in uveal melanoma. However, success with these treatments in OM has been limited so far. Clinical trials are currently underway to better understand immunotherapies in OM.

Caroline Bosch-Voskens, MD gave an excellent overview of immunotherapy at the 2012 EANA Patient Retreat.

As with chemotherapy, however, the response rate within the OM population has been significantly lower than with cutaneous melanoma. The most talked about drug in this category is YERVOY™ (ipilimumab, also commonly called "Ipi"). Relatively expensive but approved for melanoma treatment as of March 2011, YERVOY is a monoclonal antibody that binds to CTLA-4, an inhibitory molecule on T lymphocytes. According to the Melanoma Research Foundation, "T lymphocytes are blood cells that may be highly effective in inhibiting cancer growth. When YERVOY binds to CTLA-4, it releases the 'brake' from the immune system and T cells can become activated to destroy tumor cells. Unfortunately, response rates in OM are not well documented."

Another promising drug is Nivolumab (Nivo, or Opdivo).  Like YERVOY, it is an immune checkpoint inhibitors that has been approved for the treatment of advanced melanoma.
Read more here about recent studies.

Other approved immunotherapy agents include cytokines which are used in the treatment of cutaneous melanoma (Interleukin-2; Interferon-alpha), dendritic cells such as those used in the treatment of prostate cancer (Provenge®).

Targeted Therapy

A form of treatment in which drugs are developed with the goal of destroying cancer cells while leaving normal cells intact. These drugs are designed to interfere with the specific molecules, genetic mutations in the tumor itself, that are driving the growth and spread of the tumor.

Targeted therapy is where drugs are developed specifically with the goal of destroying cancer cells while (hopefully) leaving normal cells intact. These bespoke and often expensive drugs are custom cocktails designed to interfere with the specific molecules driving tumor growth. Since they are custom crafted to the tumor, these types of therapies are generally more effective and have fewer side effects versus chemotherapy. Taking a targeted approach to systemic OM treatment also allows the classification of the disease into different subtypes based on the tumor's genetic profile, allowing personalized drug treatment. As an example, 50% of cutaneous melanomas have a BRAF mutation and respond to BRAF inhibitors but, unlike melanomas on the skin, OM does not express a BRAF mutation and so will not respond to a BRAF inhibitor. The most common mutations in uveal melanoma are the GNAQ, GNA11 and BAP1 genes and about 80% of ocular melanomas express either the GNAQ or GNA11 mutations and studies are ongoing to identify what targeted therapies will work in these mutations.

Chemotherapy

Overall, chemotherapy has not been shown to be effective for OM. However, it may still be recommended in some cases.