Treatment Options for Stage IV Melanoma

Once your stage of melanoma has been determined, your doctor will discuss a treatment plan with you. Several new drugs have been approved by the FDA, and have shown improvements in survival. Many experimental treatments are also under investigation and may be available by enrolling in a clinical trial.


The purpose of the surgery is to remove the cancerous tumors or lymph nodes that have metastasized or spread to other areas of the body, if they are few in number and/or are causing symptoms.

Learn more about surgery

Treatment Options

Treatment given in addition to a primary cancer treatment (such as surgery) is recommended for Stage IV melanoma. These are systemic therapies that go through the bloodstream to reach and affect cancer cells throughout the body. The goal of systemic treatment is to try and control the melanoma and treat symptoms. Treatments can be divided into immunotherapies, targeted therapies, and chemotherapy.


IMLYGIC (talimogene laherparepvec "T-Vec")

Purpose and Effectiveness

  • Imlygic is a genetically modified live oncolytic herpes virus designed to replicate within cancer cells and produce an immunostimulatory protein called GM-CSF (granulocyte-macrophage colony-stimulating factor).
  • In a Phase III study, 16.3 percent of patients treated with Imlygic had a decrease in the size of their skin and lymph node lesions lasting for at least six months, compared to 2.1 percent of patients treated with GM-CSF).
  • In the study, the median time to response was 4.1 months in the Imlygic arm. Imlygic has not been shown to improve overall survival or to have an effect on melanoma that has spread to the brain, bone, liver, lungs, or other internal organs.

Learn more about Imlygic

KEYTRUDA (pembrolizumab)

Purpose and Effectiveness 

  • Keytruda is designed to block a cellular target known as PD-1, which restricts the body’s immune system from attacking melanoma cells. It works by increasing the ability of the body’s immune system to fight advanced melanoma.
  • In a large Phase 1 clinical trial, half of the participants received Keytruda at the recommended dose of 2 mg/kg. Of these patients, approximately 24% had their tumors shrink. This effect lasted at least 1.4 to 8.5 months and continued beyond this period in most patients.

Learn more about Keytruda

OPDIVO (nivolumab)

Purpose and Effectiveness

  • Opdivo is a humanized monoclonal antibody. It is designed to block a cellular target known as PD-1, which results in an anti-tumor immune response.
  • The approval of Opdivo was based on the results of a Phase III clinical trial of 120 patients with unresectable (cannot be removed by surgery) or metastatic (advanced) melanoma. Of these patients 32 percent had a response to Opdivo. This effect lasted for more than six months in approximately one-third of the patients. Responses to Opdivo were demonstrated in both patients with and without the BRAF V600 mutation.

Learn more about Opdivo

PROLEUKIN / IL-2 (interleukin-2)

Purpose and Effectiveness 

  • Proleukin/IL-2 is designed to restore and strengthen the immune system.
  • This treatment shrinks tumors in about 16% of patients, of which 6% appear to derive long term durable responses.

Learn more about Proleukin/IL-2

YERVOY (ipilimumab)

Purpose and Effectiveness 

  • Yervoy is designed to restore and strengthen the immune system by successfully activating T-cells (T lymphocytes), a critical component of the immune system, with the hope of sustaining an active immune response to fight the cancer cells for a long time.
  • Studies indicate that Yervoy improves overall median survival by 4 months compared to a vaccine treatment. In a 2013 analysis from 12 prospective and retrospective studies it was shown that the median overall survival for patients treated with Yervoy was 11.4 months. Among these patients, 22% were still alive after three years. There were no deaths among patients who survived beyond seven years, at which time the overall survival rate was 17%.

Learn more about Yervoy

Targeted Therapies

COTELLIC (cobimetinib) and ZELBORAF (vemurafenib) Combination

Purpose and Effectiveness 

  • Cotellic in combination with Zelboraf blocks a cellular pathway to inhibit the growth of melanoma tumors.
  • In a phase III trial that compared, Cotellic in combination with Zelobraf to Zelboraf alone, progression-free survival (the time a patient lives without cancer growing or spreading) was 12.3 months for patients treated with the combination, versus 7.2 months for patients treated with Zelboraf alone.
  • Patients taking Cotellic plus Zelobraf lived longer (overall survival), with approximately 65 percent of patients alive 17 months after starting treatment as compared to half of those taking Zelobraf alone.

Learn more about Cotellic in combination with Zelobraf

MEKINIST (trametinib) and TAFINLAR (dabrafenib) Combo

Purpose and Effectiveness

  • In patients with a BRAF mutation, Tafinlar in combination with Mekinist blocked the cellular pathway to inhibit the growth of melanoma metastases.
  • In a phase III trial comparing Tarinlar in combination with Mekinist versus Zelboraf alone in patients with BRAF V600E or V600K mutations, the combination group had a progression free survival of 11.4 months compared to 7.3 months in the Zelboraf only group.

Learn more about Mekinist in combination with Tafinlar

MEKINIST (trametinib)

Purpose and Effectiveness

  • Mekinist blocks a cellular pathway to stop the growth of melanoma tumors.
  • In a trial comparing trametinib to chemotherapy (dacarbazine or paclitaxel) in patients with metastatic melanoma with a BRAF V600E or V600K mutation, the trametinib group had improved overall survival compared with chemotherapy.
  • Mekinist has not shown to benefit patients who have already taken another BRAF inhibitor and is only used alone in patients who cannot take Zelboraf or Taflinar.

Learn more about Mekinist

TAFINLAR (dabrafenib)

Purpose and Effectiveness

  • Tafinlar blocks a cellular pathway to stop the growth of melanoma tumors.
  • In a trial comparing Tafinlar to chemotherapy in patients with the BRAF V600E mutation, the Taflinar group had progression free survival (the time a patient lives without cancer growing or spreading) of 6.9 months compared to 2.7 months for those on chemotherapy.

Learn more about Tafinlar

ZELBORAF (vemurafenib)

Purpose and Effectiveness

  • The BRAF protein is normally involved in regulating cell growth, but is mutated (abnormal) in about half of patients with late-stage melanomas. Vemurafenib and dabrafenib work by blocking the function of the V600E-mutated BRAF protein.
  • In a trial comparing Zelboraf to chemotherapy in patients with the BRAF V600E mutation, the chemotherapy group had a median survival time of 9.7 months, with 44% still living at one year. Median survival time in the Zelboraf group was 13.6 months, with 56% still living at one year.

Learn more about Zelboraf


DTIC (dacarbazine)

Purpose and Effectiveness

  • DTIC is given to shrink or slow the growth of melanoma tumors that have spread throughout the body.
  • It appears to benefit approximately 5-20% of patients with disease shrinkage. It has not been shown to change overall survival.

Learn more about DTIC

Radiation Therapy

Radiation is used in some situations to slow tumor growth or shrink a tumor in organs where surgery is not possible or is not recommended. It is also used to relieve symptoms caused by tumors, such as in the brain or bone.

Learn more about radiation therapy

Clinical Trials

Clinical trials are research studies to evaluate new therapies and improve cancer care. These studies are responsible for most of the advances in cancer prevention, diagnosis, and treatment. If you have melanoma, you may be eligible to participate in a clinical trial.

Several experimental treatments are currently being tested in clinical trials.

  • Immunotherapies: designed to boost the body’s immune response to tumors. Ongoing clinical trials include anti-CTLA-4, PD1, and PD-L1, as well as other immunotherapies.
  • Targeted Therapies: designed to inhibit mutations and pathways that promote the growth and survival of tumor cells. Some clinical trials are designed for patients with specific mutations in their tumors (for example, BRAF), and thus require testing to determine if patients are appropriate for a given therapy.
  • Vaccines
  • Adoptive Cell Transfer [ACT]: the transfer of immune cells that have been selected or engineered to attack tumors, particularly with tumor infiltrating lymphocytes [TIL].
  • Chemotherapy
  • Combinations: trials to combine different systemic treatments, as well as trials to test whether combining systemic treatments with surgery, radiation, and other therapies can improve outcomes in patients.

In addition to performing clinical trials to test the safety and effectiveness of new treatments, many investigators are also working to determine why therapies work in some patients but not in others, as well as why they sometimes stop working after initial success.  This research depends on the participation of patients in clinical trials, and sometimes in parallel studies that allow researchers to analyze samples of blood, tumor tissue, or other materials.  Some studies have the potential to help patients who currently have melanoma, but also to help melanoma patients in the future.

Learn more about clinical trials

Find a Melanoma Specialist

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