Targeted Therapy Drugs for Melanoma Skin Cancer

Targeted drugs are designed to attack parts of melanoma cells that make them different from normal cells. Targeted drugs can be very helpful in treating advanced melanomas when the cancer cells have certain gene changes.

Biomarker testing

If you have melanoma that has spread beyond where it started, a biopsy will likely be taken to see if the cancer cells have certain gene changes (mutations). This is known as biomarker testing.

If certain gene changes are present, targeted drugs might be treatment options.

Drugs that target cells with BRAF gene changes

About half of all melanomas have changes in the BRAF gene. Melanoma cells with these changes make an altered BRAF protein that helps them grow.

Drugs that target the BRAF protein, called BRAF inhibitors, or that target the related MEK proteins, called MEK inhibitors, can often be helpful in treating these melanomas, although they aren’t likely to work on melanomas that have a normal BRAF gene.

Most often, if a person has a BRAF gene change and needs targeted therapy, they will get both a BRAF inhibitor and a MEK inhibitor, as combining these drugs often works better than either one alone. Combining these drugs also lowers the risk of some side effects, such as the development of other skin cancers.

BRAF inhibitors

Vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi) are drugs that target the BRAF protein.

These drugs can often be helpful for people whose melanoma has spread or can’t be removed completely.

Dabrafenib can also be used along with the MEK inhibitor trametinib after surgery in people with stage III melanoma, where it can help lower the risk of the cancer coming back.

These drugs are taken as pills or capsules, typically once or twice a day.

Possible side effects of BRAF inhibitors

Common side effects of these drugs can include skin thickening, rash, itching, sensitivity to the sun, headache, fever, joint pain, fatigue, hair loss, and nausea.

Less common but serious side effects can include heart rhythm problems, liver problems, kidney failure, severe allergic reactions, severe skin or eye problems, bleeding, and increased blood sugar levels.

Some people treated with these drugs develop new squamous cell skin cancers. These cancers are usually less serious than melanoma and can be treated by removing them. Your doctor will want to check your skin often during treatment and for several months afterward. You should also let your doctor know right away if you notice any new growths or abnormal areas on your skin.

MEK inhibitors

Drugs that block MEK proteins can also help treat melanomas with BRAF gene changes. MEK inhibitors include trametinib (Mekinist), cobimetinib (Cotellic), and binimetinib (Mektovi).

These drugs can be used to treat melanoma that has spread or can’t be removed completely.

Trametinib can also be used along with dabrafenib after surgery in people with stage III melanoma, where it can help lower the risk of the cancer coming back.

MEK inhibitors are pills taken once or twice a day.

Possible side effects

Common side effects of these drugs can include rash, nausea, diarrhea, swelling, and sensitivity to sunlight.

Rare but serious side effects can include heart, lung, or liver damage; bleeding or blood clots; vision problems; muscle damage; and skin infections.

Drugs that target cells with C-KIT gene changes

A small portion of melanomas have changes in the C-KIT gene that help them grow. These changes are more common in melanomas that start in certain parts of the body, including:

• On the palms of the hands, soles of the feet, or under the nails, known as acral melanomas
• Inside the mouth, throat, or the genital or anal area, known as mucosal melanomas
• In areas that get chronic sun exposure

If you have an advanced melanoma that started in one of these places, your doctor might test to see if your melanoma cells have changes in the C-KIT gene. If so, a targeted drug such as imatinib (Gleevec), dasatinib (Sprycel), or nilotinib (Tasigna) might be helpful.

Drugs that target cells with other gene changes

Rarely, melanomas have changes in other genes that can be targeted with certain drugs. Tests might be done on the melanoma cells to look for changes in genes such as:

• NRAS
• ALK
• ROS1
• NTRK

These gene changes aren’t common in melanomas, but some targeted drugs might be a treatment option if a change in one of these genes is found.

Drugs that target other gene changes are also being studied in clinical trials.