Targeted therapy is the use of medicines that target the parts of cancer cells that make them unlike normal cells. Targeted medicines for melanoma work on genes and proteins in melanoma cells. Targeted medicines are different from standard chemotherapy medicines. They can work when chemotherapy medicines don’t. And they have different side effects.
What targeted therapy medicines are used for melanoma?
BRAF inhibitors
BRAF is a gene that’s part of body cells. About 50% of all melanomas have changes in the BRAF gene. These changes help the melanoma cancer cells grow. Some medicines can target this BRAF gene with V600 mutations to help attack melanoma. Before the medicines are used, a sample of melanoma tissue is tested for change in the BRAF gene. Melanoma cells that don’t have a change in the BRAF gene would not be helped by these targeted medicines.
Vemurafenib, dabrafenib, and encorafenib are medicines that target the BRAF gene. These are used to treat advanced melanomas that can’t be removed with surgery. They can often shrink tumors for at least several months. The medicine is taken daily as pills or capsules.
The most common side effects of these medicines include:
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Skin rashes
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Skin thickening
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Sun sensitivity
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Joint pain
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Feeling tired (fatigue)
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Nausea
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Fever
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Hair thinning
In some cases, these medicines can cause squamous cell carcinoma. This is a less serious type of skin cancer that can be easily treated with surgery. Less common but more serious side effects are also possible. Talk with your healthcare provider about the risks and benefits of these medicines for you.
MEK inhibitors
A protein in cells called MEK can interact with the BRAF protein to help melanoma cells grow. There are three medicines that target MEK proteins. The medicines are called MEK inhibitors. They are trametinib, cobimetinib, and binimetinib. MEK inhibitors are taken daily as a pill to help treat advanced melanomas. They are only helpful for people whose melanoma cells have BRAF gene changes. When used alone, MEK inhibitors do not shrink tumors as well as a BRAF inhibitor. But when used with a BRAF inhibitor, they may work better than either medicine alone. Also, combining a BRAF inhibitor and a MEK inhibitor may lower the risk of getting other skin cancers that can be caused by a BRAF inhibitor.
The most common side effects of MEK inhibitors include:
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Rash
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Diarrhea
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Swelling
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Sun sensitivity
Some other side effects are less common but can be more serious. Talk with your healthcare provider about the risks and benefits of this medicine for you.
PD-L1 inhibitor in combination with targeted therapy
Atezolizumab, a PD-L1 immune checkpoint inhibitor, is approved in combination with cobimetinib (a MEK inhibitor) and vemurafenib (a BRAF inhibitor) to treat melanoma positive with a BRAF V600 mutation. This combination of medicines is used when the melanoma can't be removed by surgery (unresectable) and when the cancer has spread to distant parts of the body (metastatic). Atezolizumab is given through an IV (intravenously) every 2 weeks, and cobimetinib and vemurafenib are taken by mouth.
The most common side effects for atezolizumab in combination with cobimetinib and vemurafenib can include:
In some cases, vemurafenib can cause squamous cell carcinoma. This is a less serious type of skin cancer that can be easily treated with surgery. Less common but more serious side effects are also possible. Talk with your healthcare provider about the risks and benefits of these medicines for you.
Tumor-agnostic treatment
The targeted therapy medicines larotrectinib and entrectinib may be used for several different types of cancer. They target a gene change called an NTRK fusion, which may be found in some melanomas. These medicines may be useful for unresectable or metastatic melanoma.
More targeted medicines being tested
Researchers continue to learn more about what makes melanoma cells different from other cells. They’re working to develop new medicines to target these differences. New medicines are being tested in clinical trials.
Researchers are also testing existing medicines to use for melanoma. A small number of melanomas have changes in the C-KIT gene that help them grow. This is most often the case for melanomas in areas such as the palms, soles of the feet, or inside the mouth. Several medicines that target C-KIT, called KIT inhibitor therapy, are already used to treat some other types of cancers. These medicines are now being tested in clinical trials to see if they can help treat melanomas.
If you’re interested in a medicine that is part of a clinical trial, talk with your healthcare provider. They can help you find out if a clinical trial would be right for you.
Working with your healthcare provider
It's important to know which medicines you're taking. Write your medicines down, and ask your healthcare team how they work, what side effects they might have, and when they should be reported.
Talk with your healthcare providers about what signs to look for and when to call them. Make sure you know what number to call with questions. Is there a different number for evenings, weekends, and holidays?
It may be helpful to keep a diary of your side effects. A written list will make it easier for you to remember your questions when you go to your appointments. It will also make it easier for you to work with your healthcare team to make a plan to manage your side effects.