Stage IV


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. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19

Targeted Therapy

Unlike conventional chemotherapy drugs that attack both normal and cancerous cells, targeted therapies are designed to block specific substances or pathways in cancer cells that enable cancer to grow.  A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Cancer treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes. Think of a light switch that’s stuck in the on position, as long as the switch is on, the cancer keeps growing. What these new drugs do is cut the wire or turn the switch off.  Several targeted therapies are now available for the management of malignant melanoma.

Zelboraf® (vemurafenib) was the first to be approved in a new class of drugs known as BRAF inhibitors. It turns off a genetic mutation called BRAF V600, found in about half of patients with advanced melanoma, which allows melanoma cells to grow uncontrollably. The results of a recent clinical trial demonstrated that patients taking Zelboraf® lived for nearly 16 months on average, compared with about six months for patients who took the chemotherapy drug dacarbazine. Nearly one in four patients treated with Zelboraf® developed squamous cell cancer, a type of non-melanoma skin cancer. Other common side effects included joint pain, skin rash, hair loss, and sun sensitivity.2

Tafinlar® (dabrafenib) also targets the BRAF V600 mutation. Tumor growth was delayed by about five months in patients taking Tafinlar®, compared with two to three months for patients taking dacarbazine.8Serious side effects included new skin cancers (both squamous cell and melanoma), high fever, high blood glucose, and eye inflammation. Other, more common side effects included headache, joint pain, hair loss, and redness, swelling, and pain in the hands and the feet.3

Mekinist® (trametinib) is a BRAF inhibitor that targets the BRAF mutation in a different way than Zelboraf® or Tafinlar® does. Tumor growth was delayed for about five months in patients taking Mekinist, compared with about six weeks for patients taking either dacarbazine or another chemotherapy drug, Taxol® (paclitaxel).Serious side effects included heart disease, lung diseases, and skin and eye complications. Other, more common side effects included rash, diarrhea, and swelling in the arms or legs.4

Tafinlar® plus Mekinist® The COMBI-v clinical trial compared the combination of the BRAF inhibitor Tafinlar® plus the MEK inhibitor Mekinist® with Zelboraf® alone in 704 patients with the BRAF V600 mutation.  Overall response rates, duration of response and overall survival were improved with combination therapy. The median overall survival was 17.2 months with Zelboraf® alone and had not been reached in the Tafinlar®/ Mekinist® treated patients.5

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