Stage IV Melanoma


Patients with stage IV, or metastatic, melanoma have cancer that has spread from its site of origin to distant lymph nodes or other distant sites in the body, such as the liver, lungs, or brain.

The following is a general overview of the treatment of stage IV melanoma. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Treatment for stage IV melanoma is generally directed at slowing the growth of the cancer and prolonging survival. Treatment options for advanced melanoma have expanded greatly in recent years, and promising new drugs continue to be developed and tested.

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Immunotherapy refers to treatments that activate the immune system to recognize and fight against cancer cells. This has proven to be an important strategy against melanoma.

Yervoy® (ipilimumab) is an immunotherapy drug that was approved for the treatment of advanced melanoma in 2011. It targets a molecule known as CTLA4 that is found on the surface of T cells. CTLA4 inhibits immune responses, and by targeting this molecule, Yervoy may enhance the immune system’s response against tumor cells. Treatment with Yervoy has been shown to prolong overall survival in patients with metastatic melanoma.1 Potential side effects of Yervoy include autoimmune reactions (immune responses against the body’s own tissues).

Proleukin® (IL-2): Given in high doses, IL-2 can slow or stop the growth of metastatic melanoma in some patients.High doses of this drug, however, are associated with serious side effects. IL-2 can be administered as a single therapy and is also available in clinical trials combined with other promising treatments.

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Targeted drugs interfere with specific biologic pathways that contribute to cancer growth. They have the potential advantage of sparing the patient from unwanted side effects. The goal is to target the cancer directly, while avoiding healthy cells.

In the case of advanced melanoma, mutations in the BRAF gene are found in roughly half of all patients. These mutations produce abnormal proteins that contribute to melanoma growth. Zelboraf® (vemurafenib) and Tafinlar® (dabrafenib) are BRAF inhibitors that slow melanoma growth. They are used only for patients whose cancers contain a particular BRAF mutation known as the V600E mutation.

Mekinist® (trametinib) is another targeted therapy that improves outcomes in selected patients with advanced melanoma. It is a type of drug known as a MEK inhibitor, and it is used for patients whose cancers contain either the V600E or the V600K mutation of the BRAF gene. Mekinist® can be used in combination with Tafinlar®.

Patients with metastatic melanoma may wish to ask their physicians about BRAF mutation testing and how it can guide subsequent treatment.


Dacarbazine, temozolomide, paclitaxel, and carboplatin are chemotherapy drugs that may be used for the treatment of metastatic melanoma. With the introduction of newer and more effective immunotherapies and targeted therapies, chemotherapy is playing less of a role in the initial treatment of metastatic melanoma.


Although surgery has a somewhat limited role in the treatment of metastatic melanoma, it can be useful for treating very limited areas of cancer spread in organs such as the lungs or brain. This can help to relieve symptoms, and may also prolong survival.  Surgical removal of melanoma may also be helpful when combined with other biologic or targeted therapies because it reduces the amount of cancer in the body, potentially making it easier for these therapies to be beneficial.


Radiation therapy can relieve symptoms, especially pain from cancer that has spread to the bone. Radiation therapy may also be used to shrink melanoma that has spread to the brain.


The progress that has been made in the treatment of melanoma has resulted from improved development of treatments in patients with more advanced stages of cancer and participation in clinical trials. Future progress in the treatment of melanoma will result from continued participation in appropriate clinical trials. Currently, there are several areas of active exploration aimed at improving the treatment of melanoma.

New Immunotherapy Drugs: Investigational immunotherapy drugs known as anti-PD-1 drugs have produced very promising response rates in early-phase clinical trials. These drugs include pembrolizumab and nivolumab.2,3

New Targeted Therapies: Melanoma of the eye—also known as uveal melanoma—is a rare cancer that affects approximately 2,000 people each year in the United States. Although the cancer is often diagnosed at an early stage, roughly half of patients subsequently develop advanced, difficult-to-treat disease.

A majority of cases of melanoma of the eye involve mutations in the Gnaq or Gna11 genes. These mutations activate a biological pathway that contributes to cancer growth. An investigational drug known as selumetinib blocks a protein—MEK—that is necessary to the functioning of this growth pathway. Selumetinib has produced promising results against uveal melanoma in a Phase II clinical trial.4

New Sequences or Combinations of Drugs: As new drugs have been developed, it’s raised questions about how best to use them. The effectiveness and safety of drugs may depend on factors such as the order in which they’re used, whether and how they’re combined with other drugs, and whether they’re used continuously or intermittently. These are active areas of research.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Managing Side Effects.


1. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. Jun 30 2011;364(26):2517-2526.

2. Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (Anti-PD-1) in melanoma. N Engl J Med. Jun 2 2013.

3. Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. Jun 2 2013.

4. Carvajal RD, Sosman JA, Quevedo F. Phase II study of selumetinib (sel) versus temozolomide (TMZ) in gnaq/Gna11 (Gq/11) mutant (mut) uveal melanoma.Presented at the 49th Annual Meeting of the American Society of Clinical Oncology. May 31-June 4, 2013; Chicago, IL. Abstract CRA9003.


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