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As many as half of people diagnosed with uveal melanoma (ocular melanoma) go on to have what’s called metastatic disease. Most often, the cancer metastasizes (spreads) beyond the eye to the liver, but it can also spread to the lungs, bone, and skin. Rarely, it can go to the lymph nodes or brain.

What Are Treatments for Metastatic Uveal Melanoma?

There are no standard treatments once uveal melanoma has spread, but research is continuing and there is hope. Some treatments are:

Immunotherapy

Immunotherapy, treatment that uses your own immune system, seems fairly new to medicine, but scientists have known about it for over a century. The medical community didn’t pay much attention to its potential until the 1980s, when serious research into using immunotherapy to treat cancer began.

A new immunotherapy drug, tebentafusp (Kimmtrak), was approved by the FDA in January 2022. Tebentafusp is given by IV (through a vein) once a week. In clinical trials, the drug cut the risk of death from metastatic uveal melanoma by half. But it does come at a cost. It’s estimated that it costs between $400,000 and $500,000 for a year’s course of treatment.

Side effects can include:

  • Skin issues (itching, rash, redness, swelling)
  • Headache
  • Fever
  • Fatigue
  • Nausea and vomiting
  • Abdominal pain
  • Low blood pressure
  • Abnormal liver function tests
  • Cytokine release syndrome (overactivity of the immune system)

Pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy) are checkpoint inhibitors, also immunotherapy drugs. These don’t seem to be as helpful in uveal melanoma treatment, so they aren’t used often, but some people do get good results.

Possible side effects for these drugs are similar to those caused by tebentafusp (skin rash, fatigue, nausea), as well as:

  • Cough
  • Poor appetite
  • Constipation or diarrhea
  • Joint pain
  • Allergic reactions

If you take a checkpoint inhibitor, you also have a risk of autoimmune reactions. These happen when your immune system goes into overdrive and starts to attack your organs, such as the liver, intestines, kidneys, and others.

The last group of drugs in this category is targeted drugs. Targeted therapy zeroes in on specific types of cancer cells. But it doesn’t damage surrounding healthy cells like chemotherapy can. Not many patients with metastatic uveal melanoma have the type of cell mutations the therapy targets, so the drugs might not be as useful.

Radiation

Radiation therapy can be used to treat metastases – tumors that spread to other parts of the body. Radiation used to be considered a “salvage” therapy – a last ditch attempt to help shrink the metastases. Early studies now show giving radiation therapy sooner is promising. But more research is needed.

Chemotherapy

Chemotherapy, medication that kills or disrupts cancer cells so they can’t reproduce, is not a common choice for metastatic uveal melanoma treatment.

Researchers have studied many chemotherapy drugs used alone or in combination with others, but the patients with metastatic uveal melanoma don’t often respond as well as people who have other types of cancer. That being said, some oncologists will try certain types of chemotherapy, most often dacarbazine (DTIC) by IV or temozolomide, which is in a pill form.

Laser therapy

Laser therapy is a treatment that destroys blood vessels around a cancerous tumor so it can’t get the nutrients it needs to grow. It might be considered to help treat metastatic uveal melanoma, but it is not common. The therapy might be used to target liver metastases. Laser therapy doesn’t provide a cure, but it may extend life by a few years, according to some studies.

Surgery and ablative procedures

Surgery or ablation may be other options for liver metastases treatment. But they, too, are not commonly performed. With surgery, a surgeon makes an incision and removes the tumors. Ablation uses different techniques – radiofrequency ablation, cryotherapy, or stereotactic radiation – to remove or destroy the tissue.

  • Radiofrequency ablation (RFA) involves inserting a needle through your skin to the liver, targeting the tumor. Once in place, electrical currents heat the needle, destroying the cancer cells. It is also called microwave ablation.
  • Cryotherapy is the opposite of RFA. It uses extreme cold to destroy the cancer cells. A surgeon inserts a narrow probe through your skin to the liver tumor. Liquid gas moves through the probe to freeze the tumor.
  • Stereotactic radiation is a type of radiosurgery, but instead of making an incision, high doses of radiation target the metastases, making them unable to reproduce.

Possible side effects from surgical and ablation treatments include:

  • Fatigue
  • Swelling
  • Skin or scalp sensitivity
  • Liver damage
  • Infection
  • “Flu-like” symptoms
  • Bleeding

Which Treatment Is Best for Metastatic Uveal Melanoma?

Choosing which treatment is best for you depends on many things, from where the cancer has metastasized, how far it is from the eye, to your overall health.

When deciding on immunotherapy, your doctor will want to know if you have human leukocyte antigen (HLA)-A*02:01. Antigens are substances that bring on an immune response in your body. If you do have this antigen, you have a higher chance of responding to tebentafusp before trying other therapies.

Clinical trials may also be an option. Speak with your oncologist about clinical trials in your area (or elsewhere if you are willing and able to travel). Trials give patients an opportunity to try new therapies or combinations of therapies.

© 2022 WebMD, LLC. All rights reserved.

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SOURCES:

American Cancer Society: “Immunotherapy and Targeted Drugs for Eye Cancer,” “Immunotherapy for Melanoma Skin Cancer.”

Cancer Research Institute: “Immunotherapy Fact of the Day #2.”

Clinical Cancer Research: “The Latest on Uveal Melanoma Research and Clinical Trials: Updates from the Cure Ocular Melanoma (CURE OM) Science Meeting (2019).”

ClinicalTrials.gov: “Metastatic Uveal Melanoma.”

HPB: “Systematic review of liver directed therapy for uveal melanoma hepatic metastases.”

Journal of Nuclear Medicine: “First-Line Selective Internal Radiation Therapy in Patients with Uveal Melanoma Metastatic to the Liver.”

Journal of the Advanced Practitioner in Oncology: “Immunotherapy Through the Years.”

Journal of the European Academy of Dermatology and Venereology: “MR-guided laser-induced thermotherapy (LITT) in patients with liver metastases of uveal melanoma.”

Mayo Clinic: “Stereotactic radiosurgery.”

Memorial Sloan Kettering Cancer Center: “New Drug Shows Promise for Treating Eye Cancer Called Uveal Melanoma.”

National Cancer Institute: “Ablation,” “Cryosurgery to Treat Cancer,” “Antigen.”

Ocular Melanoma Foundation: “Treatment of Metastatic Disease.”

RadiologyInfo.org: “Radiofrequency Ablation (RFA)/Microwave Ablation of Liver Tumors.”

The British Journal of Ophthalmology: “Metastatic disease from uveal melanoma: treatment options and future prospects.”

ThePharmaLetter: “Despite hefty price, Immunocore’s Kimmtrak will dominate uveal melanoma market.”

U.S. Food & Drug Administration: “FDA approves tebentafusp-tebn for unresectable or metastatic uveal melanoma.”

UpToDate: “Management of metastatic uveal melanoma.”