Targeted Drugs & Immunotherapy for Melanoma

Doctors at NYU Langone’s Perlmutter Cancer Center often prescribe targeted medications for advanced melanoma, in which the cancer has spread beyond the skin to other parts of the body. Targeted drugs include kinase inhibitors and immunotherapies.

Kinases are proteins that are involved in regulating cell growth. Healthy versions of these proteins signal cells to grow and divide in a controlled manner. Changes in genes can cause that signaling process to go awry. Altered kinases send signals that make a cell grow uncontrollably, leading to cancer.

About 50 percent of people with melanoma have mutations in a gene called BRAF, interfering with the cell signaling process. BRAF inhibitors block the altered kinases, helping to slow the growth of melanoma. Examples of these medications are vemurafenib and dabrafenib. Both are taken by mouth daily and may be used for as long as they appear to be working.

While these medications can act very quickly to shrink melanoma tumors, this response lasts for only about a year. That’s why doctors at Perlmutter Cancer Center may add another type of kinase inhibitor called trametinib to treatment with either vemurafenib or dabrafenib.

This medication, which is taken by mouth daily, blocks a protein called MEK, which is part of the BRAF cell signaling pathway, a chain of events that controls cell growth. Adding drugs that target MEK may keep melanoma under control for a longer period.

Immunotherapies encourage the body’s immune system to attack cancer cells. The medication ipilimumab is a monoclonal antibody, meaning it’s made of an immune system protein that targets and helps destroy foreign substances. These antibodies bind to another protein, which boosts the immune system’s response to melanoma cells.

About 11 percent of people with melanoma that has spread respond to this drug, meaning the tumor shrinks. Some stay in remission, meaning doctors cannot detect any signs or symptoms of the melanoma, for years. Some remain free of cancer the remainder of their lives. Ipilimumab is given as an intravenous (IV) infusion once every three weeks for several treatments.

People receive a combination of ipilimumab and nivolumab, monoclonal antibody medications that target a protein to improve the body’s immune response to melanoma by encouraging disease-fighting white blood cells, called T cells, to become more active. Melanoma shrinks in more than 50 percent of people given this combination of drugs.

Doctors may prescribe another monoclonal antibody medication called pembrolizumab, which also binds to proteins on the surface of cancer cells, making them more vulnerable to T cell activity. The medication can be given to people who have melanoma that grows after receiving ipilimumab. Pembrolizumab is given by IV infusion through a vein, usually once every three weeks. Melanoma shrinks in about 40 percent of people given this drug.

Together, these immunotherapies can boost the immune system and make cancer cells more susceptible to a T cell attack.

Joint pain, skin rash, and itching are common side effects of kinase inhibitors, while skin rash, itching, fatigue, and diarrhea are associated with immunotherapy. Doctors can adjust the dose of these medications, substitute others, or prescribe integrative health therapies to help manage side effects.

At Perlmutter Cancer Center, people with advanced melanoma are usually considered for a clinical trial before they are given targeted medications or immunotherapies. Clinical trials offer people who have melanoma the chance to try combinations of newer medications, which may be more effective than standard treatment.

Researchers are exploring new treatments for melanoma that has spread to the brain and new medications for melanoma that is resistant to BRAF inhibitor. They are also looking at biomarkers—substances in the blood that may predict a person’s response to immunotherapy.

Our doctors can help you determine whether a clinical trial is right for you.