Targeted and immunotherapy drugs for advanced melanoma skin cancer

Doctors use targeted cancer drugs or immunotherapy to treat melanoma that has spread elsewhere in the body such as the liver, lungs or bone (advanced cancer). Or to treat stage 3 melanoma that cannot be removed with surgery. Cancer that cannot be removed is called unresectable.

Doctors treat melanoma that can be removed with surgery (resectable) differently.

What are targeted cancer drugs and immunotherapy?

Targeted cancer drugs work by targeting the differences in cancer cells that help them to grow and survive. Other drugs help the immune system to attack the cancer. They are called immunotherapies.

When do you have targeted cancer drugs and immunotherapy?

Your doctor normally gives you targeted cancer drugs and immunotherapy to treat advanced melanoma. This is also called metastatic or stage 4 melanoma.

The treatment for unresectable stage 3 melanoma skin cancer is the same as the treatment for advanced melanoma. Stage 3 means the melanoma has spread to:

• an area between the melanoma and the nearby lymph nodes
• the lymph nodes close to where the melanoma started

The aim of treatment is to control the cancer and help any symptoms. For some people, melanoma may be controlled for years after treatment.

If you need targeted cancer drugs or immunotherapy, which ones you have depends on:

• any cancer drugs you have already had for the melanoma
• if there are changes in the cancer genes
• your general health

Tests on the cancer cells

Your doctor sends a sample of the melanoma for genetic testing. The test looks for changes in the cancer such as changes to the BRAF gene. Changes in this gene can make the melanoma cells grow.

About 40 to 50 out of every 100 people with skin melanoma (40 to 50%) have a change in the BRAF gene.

If you don’t have changes in the BRAF gene, then the melanoma is BRAF negative. This is also called BRAF wild type. Doctors use immunotherapy to treat BRAF negative melanoma skin cancer.

If there are changes in the BRAF gene, doctors describe the melanoma as BRAF positive. This is also called BRAF mutated. Doctors can use targeted cancer drugs or immunotherapy to treat BRAF positive melanoma skin cancer.

BRAF negative melanoma skin cancer

Your doctor normally recommends treatment with a type of immunotherapy drug called a checkpoint inhibitor. These block proteins on the cancer cells that stop the immune system from attacking them. The checkpoint inhibitors used to treat advanced and unresectable melanoma are:

• ipilimumab (Yervoy)
• pembrolizumab (Keytruda)
• nivolumab (Opdivo)

Or you might have a combination of immunotherapy drugs such as:

• nivolumab and ipilimumab
• nivolumab and relatlimab - this combination is called Opdualag

You have immunotherapy as a drip into your bloodstream (intravenously).

BRAF positive melanoma skin cancer

Doctors can use targeted cancer drugs or immunotherapy to treat BRAF positive melanoma skin cancer.

Targeted cancer drugs

BRAF positive melanoma produces too much of a protein called BRAF. This also affects other proteins such as MEK.  Both of these can make the cancer grow. Targeted cancer drugs work by blocking the proteins. This slows or stops the growth of the cancer cells. These are called cancer growth blockers or inhibitors.

You usually have a BRAF protein inhibitor with a MEK protein inhibitor. This is because they work better together.

You normally have treatment with either:

• dabrafenib (Tafinlar) and trametinib (Mekinist)
• encorafenib (Braftovi) and binimetanib (Mektovi)

Dabrafenib and encorafenib are BRAF inhibitors. And trametinib and binimetanib are both MEK inhibitors.

You take these as tablets or capsules.

Immunotherapy

Some people may have immunotherapy instead of targeted cancer drugs. This is normally one of the following:

• ipilimumab 
• pembrolizumab
• nivolumab

Or you might have a combination of immunotherapy drugs such as:

• nivolumab and ipilimumab
• nivolumab and relatlimab - this combination is called Opdualag

A nurse gives you immunotherapy as a drip into your bloodstream (intravenously).

Immunotherapy into the melanoma

Doctors might use another type of immunotherapy called talimogene laherparepvec (T-VEC). They inject this straight into the melanoma. It’s a weakened form of the cold sore virus. The virus has been changed so it grows in the cancer cells and destroys them. It works by helping the immune system recognise and attack cancer cells. 

You might have T-VEC for melanoma that can’t be removed with surgery and has spread to the lymph nodes. It may also have spread to another area of skin or soft tissue away from the original (primary) melanoma. Soft tissue includes:

• muscles
• nerves
• fat
• blood vessels

T-VEC treats the melanoma it is injected into. But it may also have an effect on any areas of melanoma that have spread nearby.

Side effects

Everyone is different and side effects can vary from person to person. The side effects you may have depend on:

• which cancer drug you have
• whether you have it alone or with other cancer drugs
• the amount of the cancer drug you have (the dose)
• your general health

A side effect may get better or worse during the course of your treatment. Or more side effects may develop as the treatment goes on.

Immunotherapy drugs may cause inflammation in different parts of the body. These can cause serious side effects. They could happen during treatment, or some months after treatment has finished. In some people these side effects could be life threatening.

T-VEC side effects

Having T-VEC may cause side effects like other immunotherapy drugs. But it can also cause a reaction at the injection site. This can make the area painful, red, bleed, swell and feel warm. It can also cause a leak of fluid or discharge from the site. 

For more information about the side effects of your treatment, see the individual drug pages.

Clinical trials

Sometimes your doctor might talk to you about having your treatment as part of a clinical trial. Doctors and researchers do trials to make existing treatments better and develop new treatments.

Researchers continue to look at new targeted and immunotherapy drugs to treat advanced melanoma. They are also looking at different combinations of drugs.