What Medications Are Used to Treat Melanoma?

Skin cancer is the most common type of cancer in the U.S. Melanoma only makes up a small percentage of cases, but it causes the most skin cancer deaths. And the rates of new melanoma cases have gone up over the past few decades. 

Surgery is usually the first step in treating melanoma, if it’s able to be removed. Medications may be used before surgery to shrink the tumor and make it easier to remove. They can also be given afterwards to lower the chance of it coming back. In other cases, they may be used if the melanoma can’t be removed or if it has spread to other parts of the body (metastatic melanoma).

Several different types of medications are available to treat melanoma. When and how they’re used depends on the stage of the melanoma and your specific situation. Read on to learn more about these treatments and how they work.

Immunotherapy for melanoma

Immunotherapy works by making your immune system better at finding and attacking cancer cells. There are a few types of immunotherapy, and they each work in slightly different ways to treat melanoma. These include:

• Immune checkpoint inhibitors

• Immunomodulators

• Adoptive cell therapy

• Oncolytic viral therapy

Depending on your specific situation, your oncologist will decide if and how immunotherapies may be used to treat your melanoma.

Common immunotherapy side effects include rashes, diarrhea, and feeling tired. Immunotherapy can also cause flu-like symptoms.

Immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) work by attaching to immune checkpoint proteins on your T cells, a type of immune cell. Some also attach to immune checkpoint proteins on tumor cells.

Immune checkpoints are proteins that help turn off T-cell activity. Their role is to keep your body’s immune system in check. But ICIs block this “off” signal, allowing T cells to attack cancer cells.

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Several ICIs are FDA approved to treat melanoma. Most are given as an intravenous (IV) infusion into a vein, but atezolizumab (Tecentriq Hybreza) and nivolumab (Opdivo Qvantig) can also be given as a subcutaneous (under-the-skin) injection. They target a few different immune checkpoint proteins to help your T cells attack cancer cells. 

Tebentafusp-tebn (Kimmtrak) is another type of immunotherapy called a bispecific antibody. It’s an option for a specific type of melanoma that affects the eye, called uveal melanoma. Kimmtrak works by attaching to both tumor cells and T cells. By bringing T cells closer to the tumor, it makes it easier for the immune system to destroy cancer cells.

Immunomodulators

Medications that boost your body’s immune response against cancer are called immunomodulators. Instead of blocking certain immune signals, like ICIs, these medications use proteins to help immune cells become more active to kill cancer cells.

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Cytokines are one important group of proteins in your immune system. Their main role is communication; they act like messengers and help tell the immune system what to do. Interleukins are a group of cytokines. One specific one, interleukin-2 (IL-2), helps boost the number and activity of white blood cells in the body. This can help the immune system kill cancer cells.

Aldesleukin (Proleukin) is lab-made IL-2 that’s used to treat melanoma. It’s given as an IV infusion in a hospital to help monitor for potentially serious side effects.

Adoptive cell therapy

Lifileucel (Amtagvi) is a type of adoptive cell therapy that uses tumor-infiltrating lymphocytes (TILs) to fight melanoma.

TILs are special because they already know how to recognize tumor cells. But without some help, they aren’t strong enough to destroy the cancer. With TIL treatment, T cells are collected from your tumor and sent to a lab to be multiplied into more TILs. This large collection of T cells is then administered back to you through an IV infusion. The idea is that a large collection of TILs is stronger and more effective against melanoma than what’s normally found in tumor cells.

Before you receive lifileucel, you’ll need to get about a week’s worth of chemotherapy so that your body can accept the cancer treatment. After lifileucel, you’ll get a few doses of IL-2 to make your TILs more effective. Like aldesleukin, this treatment can cause serious side effects and needs to be given in a hospital.

Oncolytic viral therapy

Talimogene laherparepvec (T-VEC, Imlygic) is a viral therapy that’s injected directly into a melanoma lesion if a tumor can’t be removed or comes back after surgery. 

T-VEC is a virus that’s modified in the lab. It works by copying itself in the tumor that it’s injected in. Once copied, the virus grows in the tumor and destroys cancer cells. It also helps the immune system to identify and attack future cancer cells. Modification of the virus in the lab keeps the virus focused on the cancer and prevents it from spreading to nearby healthy cells.

Targeted therapy for melanoma

Targeted therapy medications stop the growth and spread of tumor cells in a focused manner. They do this by targeting specific parts of cancer cells, like a certain protein or gene mutation (change) that’s contributing to your cancer.

Targeted therapies used to treat melanoma typically come as pills. Side effects vary depending on the medication. We’ll discuss these further below.

BRAF inhibitors

The most common mutations in melanoma are in the BRAF gene. They occur in about half of all melanomas. Mutated BRAF proteins allow cancer cells to grow out of control. By targeting BRAF-mutated cancer cells, BRAF inhibitors can slow their growth.

Three BRAF inhibitors can be used to treat melanomas that have a BRAF mutation. These include dabrafenib (Tafinlar), encorafenib (Braftovi), and vemurafenib (Zelboraf). They’re usually used in combination with MEK inhibitors (covered next) to make them work better. 

Common side effects of BRAF inhibitors include:

• Skin thickening

• Hair loss

• Rash and itching

• Sun sensitivity

• Headache

• Fever

• Joint pain

• Nausea

There are also some rare but serious side effects with BRAF inhibitor treatment. New squamous cell cancers may develop on the skin, though they’re typically removable with surgery. This side effect tends to be more common if a BRAF inhibitor is given on its own. Your oncologist should check your skin every 2 months during treatment and for up to 6 months after you stop BRAF inhibitors.

Other serious but less common side effects include:

• Heart problems

• Eye problems

• Liver or kidney problems

• High blood sugar

• High fever

• Bleeding

MEK inhibitors

When BRAF proteins are blocked, melanoma cells don’t grow well. Researchers discovered that another protein, called MEK, works closely with BRAF to help cancer cells grow. 

MEK inhibitors work by blocking MEK proteins. They’re usually given in combination with BRAF inhibitors to treat melanomas with BRAF mutations. These medications include trametinib (Mekinist), binimetinib (Mektovi), cobimetinib (Cotellic).

Common side effects of MEK inhibitors include:

• Rash

• Diarrhea

• Swelling

• Sensitivity to sunlight

The risk of developing a secondary skin cancer is less common with combination BRAF and MEK inhibitor treatment.

KIT inhibitors

Some melanomas can have a mutation in the KIT gene. This gene is partially responsible for helping cells grow and divide; mutations in KIT promote cancer cell growth.

In melanoma, these mutations happen mostly in the acral (palms of the hands, soles of the feet, under the nails) and mucosal (inside the mouth) areas of the body. They can also occur on skin that gets exposed to a lot of sun.

With melanoma, only certain types of KIT mutations are treatable with KIT inhibitors. One medication that may be considered is imatinib (Gleevec), an oral pill.

Common Gleevec side effects include:

• Swelling

• Nausea

• Muscle cramps

• Bone, muscle, or joint pain

• Diarrhea

• Rash

• Stomach pain

• Feeling tired

• Headache

Good to know: This is an off-label use for imatinib, meaning that the medication isn’t officially approved to treat melanoma. There is some research on its use for melanoma, but bigger studies (like randomized controlled trials, the gold standard for cancer research) need to be completed. Your oncologist may prescribe imatinib for melanoma at their discretion. They may also decide to use alternative KIT inhibitors, such as dasatinib (Sprycel), nilotinib (Tasigna), or ripretinib (Qinlock), instead.

Chemotherapy for melanoma

Chemotherapy medications work by killing rapidly dividing cells. They’re effective overall, but they’re known to cause troublesome side effects. Newer treatments, like immunotherapy and targeted therapies, are usually considered first. But chemotherapy may be an option after other treatments for some people.

Examples of chemotherapy medications used to treat melanoma include:

• Dacarbazine

• Temozolomide (Temodar)

• Carboplatin

• Paclitaxel

• Nab-paclitaxel

Common chemotherapy side effects include nausea and vomiting, tiredness, and nerve damage, among others. Certain chemotherapies can also cause hair loss or thinning. Temozolomide is given as an oral pill, while all other listed medications are given as IV infusions.

Keep in mind: Chemotherapy regimens are highly variable for different cancers, including melanoma. Your oncologist will determine the right regimen for you.

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Written by:

Rachel Feaster, PharmD, BCOP, BCPS

Rachel Feaster has over 10 years of professional experience in ambulatory, inpatient, pharmacogenomics, and oncology care. She is board certified in oncology and pharmacotherapy.

Written by:

Emmeline C. Academia, PharmD, BCOP

Emmeline C. Academia, PharmD, BCOP, has been a practicing clinical pharmacist in adult oncology since 2020. She is a clinical pharmacy specialist in oncology at Beth Israel Deaconess Medical Center, in Boston.

Reviewed by:

Maria Robinson, MD, MBA

Maria Robinson, MD, MBA, is a board-certified dermatologist and dermatopathologist who has practiced dermatology and dermatopathology for over 10 years across private practice, academic, and telehealth settings. She is a fellow of the American Academy of Dermatology and the American Society of Dermatopathology.

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