BRAF inhibitors
BRAF is a gene that's part of body cells. About 50% of all melanomas have changes in the BRAF gene, including "V600 mutations." These changes help the melanoma cancer cells grow. Some medicines can target this V600-mutated BRAF gene 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:
- Skin rashes.
- Skin thickening.
- Sun sensitivity.
- Joint pain.
- Feeling tired (fatigue).
- Nausea.
- Fever.
- 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 doctor 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:
- Rash.
- Diarrhea.
- Swelling.
- Sun sensitivity.
Some other side effects are less common but can be more serious. Talk with your doctor 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 I.V. (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 include:
- Skin rashes.
- Joint pain.
- Nausea.
- Diarrhea.
- Feeling tired (fatigue).
- Fever.
- Liver damage.
- Swelling of hands and feet.
- Mouth sores.
- Sun sensitivity.
- Thyroid problems.
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 doctor 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.