Targeted Drugs & Immunotherapy for Melanoma

Doctors at NYU Langone Health’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, as well as tumor-infiltrating lymphocyte (TIL) therapy.

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. This antibody binds 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, and 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 for 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.

AMTAGVI (lifileucel) is a onetime cell therapy made from a patient’s own immune cells. Perlmutter Cancer Center is a designated Authorized Treatment Center for AMTAGVI, making it one of a limited number of centers nationwide offering this therapy.

To make AMTAGVI, doctors surgically remove a piece of tumor tissue and send it to a specialized lab, where immune cells called tumor-infiltrating lymphocytes (TILs) are extracted and multiplied into billions of cells over several weeks. Before the cells are infused back into the body, patients receive a short course of chemotherapy to prepare the immune system. After the infusion, patients receive a brief course of a medication called interleukin-2 (IL-2), which helps the new cells grow and become active against the cancer.

Treatment with AMTAGVI involves a hospital stay of one to two weeks. Because these steps can cause significant side effects, care is coordinated by our multidisciplinary team experienced in cellular therapy.

AMTAGVI may be an option for adults with melanoma that cannot be removed with surgery or has spread to other parts of the body, and that has continued to grow despite treatment with immunotherapy. It may also be an option for people whose melanoma has a BRAF mutation, after treatment with a BRAF-targeted therapy.

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 inhibitors. 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.