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Treatment Options for Stage IV Melanoma

Once your stage of melanoma has been determined, your doctor will discuss a plan of treatment with you. Several new drugs, including Ipilimumab (Yervoy), Vemurafenib (Zelboraf), Dabrafenib (Tafinlar), Trametinib (Mekinist), and Dabrafenib in combination with Trametinib have been FDA approved, and have shown improvements in survival.

 

Many experimental treatments are under investigation and may be available by enrolling in a clinical trial.

 

Treatment

Goal

Surgery

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.

 

For more information on surgery click here.

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 immune or biologic therapies, molecularly targeted therapies, or chemotherapies.

 

A)     Immunotherapies

 

1)      Ipilimumab (brand name: Yervoy) is a monoclonal antibody that has been approved by the Federal Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma.

 

Purpose and Effectivenss

  • Ipilimumab is designed to restore and strengthen the immune system by specifically activating T-cells against melanoma; T cells are, a critical component of the immune system. The hope is that the immune therapy will cause a sustained and active immune response that will continue to fight the cancer cells even after the medication dosing has stopped.
  • Studies indicate that it improves overall median survival by 4 months compared to a vaccine treatment.

 

Treatment Side Effects

 

2)      High Dose Interleukin-2 (brand name: HD IL-2) is a cytokine therapy approved by the FDA for the treatment of advanced metastatic melanoma. It appears to benefit approximately 16% of patients with disease shrinkage, of which 6% appear to derive long term durable responses.

 

Purpose and Effectivenss

  • HD Interleukin-2 is designed to restore and strengthen the immune system.
  • This treatment requires that the person is in very good health with no other significant health problems, including no heart problems. Not everyone is a candidate for HD Il-2 and it is administered by trained physicians and clinical staff inside a hospital.

 

Treatment Side Effects

 

B)     Targeted Therapies

 

1)      Vemurafenib (brand name: Zelboraf) and Dabrafenib (brand name: Tafinlar) are oral kinase inhibitors that interfere with the action of mutated BRAF and have been approved by the the FDA for the treatment of patients with the BRAF V600E/K mutation with unresectable or metastatic melanoma.

 

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 vemurafenib to dacarbazine (chemotherapy) in patients with the BRAF V600E mutation, the dacarbazine group had a median survival time of 9.7 months, with 44% still living at one year. Median survival time in the Vemurafenib group was 13.6 months, with 56% still living at one year.
  • In a trial comparing dabrafenib to dacarbazine (chemotherapy) in patients with the BRAF V600E mutation, the dabrafenib 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 dacarbazine. Median overall survival in the dabrafenib group has been reported at 18.2 months, compared with 15.6 months in the dacarbazine group.

 

Treatment Side Effects

 

2)     Trametinib (brand name: Mekinist) is an oral kinase inhibitor that that interfere with the action of MEK and has been approved by the FDA for the treatment of patients with the BRAF V600E or BRAF V600K mutation with unresectable or metastatic melanoma.  Trametinib cannot be used by patients who have already used a BRAF inhibitor.

 

Purpose and Effectiveness

  • The BRAF protein is normally involved in regulating cell growth, but is mutated in about half of the patients with late-stage melanomas. Trametinib works by blocking the function of MEK, a protein that is in the same pathways as BRAF and has shown the most benefit in patients with a V600E-mutated or V600K-mutated BRAF protein.
  • In a trial comparing trametinib to dacarbazine or paclitaxel (chemotherapy) in patients with the BRAF V600E or BRAF V600K mutation, the trametinib group had progression free survival (the time a patient lives without cancer growing or spreading) of 4.8 months compared to 1.5 months for those on chemotherapy.

 

Treatment Side Effects

 

3)     Dabrafenib in combination with Trametinib

 

Purpose and Effectiveness

  • In a phase I/II trial comparing dabrafenib alone to dabrafenib with trametinib in patients with BRAF V600E or V600K mutations, the combination group had a response rate (tumor shrinkage rate) of 76% which lasted for 10.5 months versus a response rate of 54% that lasted for 5.6 months in the dabrafenib only group. There is an ongoing phase III study to evaluate the combination treatment versus single agent dabrafenib but the results are still pending at this time. The FDA granted accelerated approval for the use of combination therapy.

 

Treatment Side Effects

  • coming soon

 

C.    Chemotherapy

 

1)     Dacarbazine (brand name: DTIC) is approved by the FDA for the treatment of advanced metastatic melanomas. It appears to benefit approximately 5-15% of patients with disease shrinkage. It has not been shown to change overall survival.

 

Purpose and Effectiveness

  • Chemotherapy uses toxic drugs to destroy cancer cells. These are established and experimental systemic therapies that ago through the bloodstream to reach and affect cancer cells throughout the body.
  • Other chemotherapy medicines are also used to treat advanced melanoma.

 

Treatment Side Effects

 

To learn more about chemotherapy click here.

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, and for relieving symptoms that a particular tumor in causing, such as in the  brain or bone.

 

Radiation therapy uses x-rays to kill cancer cells.

 

For more on radiation therapy click here.

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 antibodies against CTLA4, PD1, and PD-L1, as well as other immunotherapies.
  • 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].
  • 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.
  • 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 with melanoma currently, but also to help melanoma patients in the future.

 

For more information on clinical trials click here.

 

For more information on Stage IV follow-up click here.



IMPORTANT!

All Stage IV patients should be tested for the BRAF mutations, in order to find out if they are eligible for targeted therapy or a clinical trial using targeted therapy. Some are also being tested for NRAS and c-KIT. You should discuss this testing with your doctor.

FAST FACTS

Some factors related to your Stage IV melanoma may provide a relatively more favorable outcome and help guide decisions about therapy. These include:

 

  • A limited number of sites of disease

  • The disease is limited to soft tissues and lymph nodes rather than bone and vital organs

  • Stage IV disease that does not develop until more than 1 year after treatment of earlier-stage disease

  • The occurrence of an observable and favorable response to treatment