Treatment Options for Stage III Melanoma

After your stage of melanoma has been identified, your doctor will discuss a plan of treatment with you. It is important to understand if all of your Stage III melanoma has been completely removed with surgery (resected Stage III) or if it was not possible to remove all of the melanoma (unresectable Stage III). These two variations of Stage III melanoma are treated very differently. Unresectable Stage III patients are treated similarly to Stage IV melanoma patients.

Surgery

To remove any cancer remaining after the biopsy of the primary melanoma. The procedure is called a wide local excision. Wide local incision is recommended for small, easily removable recurrent tumors and for patients with a limited number of in-transit tumors.

The surgeon removes the tumor, including the biopsy site, as well as a surgical margin, (a surrounding area of normal-appearing skin), and underlying subcutaneous tissue.

Most surgeons today follow the guidelines adopted and recommended by the National Institutes of Health and the World Health Organization Melanoma Program.

  • The recommended margins for wide local excision of the primary melanoma ranges from 1-2 cm and is determined by the thickness of the primary melanoma.
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Lymph Node Dissection

When cancerous lymph nodes are found and there is evidence that the melanoma has spread to nearby lymph nodes, an additional surgery to remove the remaining lymph nodes from the area is usually recommended. If your melanoma was found by sentinel lymph node biopsy this is called a complete lymph node dissection (CLND). If your melanoma was found because your lymph nodes were enlarged, this is called a therapeutic lymph node dissection (TLND.

The goal of the surgery is to prevent further spread of the disease through the body by way of the lymphatic system. Current studies are underway to determine whether CLND and TLND may also prolong survival.

CLND and TLND also play an important role in controlling the pain often caused by untreated lymph node disease.

Sentinel Lymph Node Biopsy (SLNB)

If a patient has already been diagnosed with Stage III melanoma, a sentinel lymph node biopsy is typically recommended only for patients where it is suspected that there might be melanoma in another lymph node basin.

The results of the biopsy will guide the course of treatment.

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Adjuvant Therapy

Systemic treatment, given after surgery to remove all the melanoma, is often recommended for Stage III melanoma. These systemic therapies go in the bloodstream in an effort to reach and destroy any remaining cancer cells throughout the body.

Immunotherapies

INTRON A (high-dose interferon alfa-2b)

Interferon is a protein produced by normal cells to fight viral infections and disease. There are now two types of interferon that have been approved by the Food and Drug Administration (FDA) for Stage III melanoma: high-dose interferon (Intron A) and pegylated interferon (Sylatron).

Purpose and Effectiveness

  • High-dose interferon is given to rev up the immune system in order to kill melanoma cells. Interferon is given to prevent the cancer from coming back after initial therapy, such as surgery.
  • When compared with patients who had no adjuvant treatment (treatment following surgery), Intron A was effective at preventing melanoma relapse. It extended the relapse free period from 0.98 years to 1.72 years. Five year-survival was 46% for those who took the drug compared to 37% for those who did not.

Treatment Side Effects

SYLATRON (peginterferon alfa-2b)

Pegylated interferon alfa-2b is designed to provide high levels of interferon in the blood when given by subcutaneous injection once a week for at least one year, and up to 5 years. This has shown to prolong disease-free survival but has not been shown to prolong overall survival.

Purpose and Effectiveness

  • Sylatron is given to rev up the immune system in order to kill melanoma cells. Sylatron is given to prevent the cancer from coming back after the initial therapy, such as surgery.
  • Sylatron is effective in delaying or preventing relapse of melanoma. The drug has not demonstrated a benefit on overall survival.

Treatment Side Effects

Clincial 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 treatments for Stage IV melanoma are currently being tested in clinical trials for Stage III.

  • Ipilimumab (Yervoy), Pembrolizumab (Keytruda), and other therapies designed to boost the immune system to fight the return of melanoma
  • Targeted therapies and targeted therapy combinations that work by blocking the function of the  mutated BRAF protein
  • Vaccines that may impove the specific immune response to melanoma
Learn more about Clinical Trials in Melanoma

Stage III Unresectable Treatments

Unresectable melanoma means that it was not possible to remove all of your melanoma. Stage III unresectable patients are treated similarly to Stage IV melanoma patients.

Surgery

See Stage III above.

Lymph Node Dissection

See Stage III above.

Sentinel Lymph Node  Biopsy (SLNB)

See Stage III above.

Adjuvant Therapy

Immunotherapies

KEYTRUDA (pembrolizumab)

Pembrolizumab (brand name: Keytruda) is a humanized monoclonal antibody that has been approved by the FDA to treat patients with unresectable or metastatic melanoma, after they have progressed on ipilimumab and, if they the carry the BRAF 600 mutation, after they have progressed on a BRAF inhibitor.

Purpose and Effectiveness 

  • It 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 pembrolizumab 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.

Treatment Side Effects 

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.
  • This indication was approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Treatment Side Effects 

YERVOY (ipilimumab)

Ipilimumab (brand name: Yervoy) is a monoclonal antibody that has been approved by the FDA (Food and Drug Administration) for the treatment of unresectable or metastatic melanoma. Unresectable melanoma is such that all sites of melanoma tumors cannot be completely removed surgically.

Purpose and Effectiveness 

  • Ipilimumab 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 it 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 ipilimumab 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%.

Treatment Side Effects 

 

Targeted Therapies

MEKINIST (trametinib) and TAFINLAR (dabrafenib) Combo

Trametinib (brand name: Mekinist) in combination with Dabrafenib (brand name: Tafinlar) has been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma with the BRAF V600E or V600K mutation.

Purpose and Effectiveness

  • The BRAF gene and protein is normally involved in regulating cell growth, but is mutated in about half of patients with melanoma.  Dabrafenib works by blocking the function of the V600E or V600K-mutated BRAF protein. Trametenib is a kinase inhibitor that works by blocking the function of the MEK protein.
  • In a phase III trial comparing dabrafenib in combination with trametinib versus vemurafenib 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 vemurafenib only group.

Treatment Side Effects 

MEKINIST (trametinib)

Trametinib (brand name: Mekinist) is a kinase inhibitor that inhibits another protein, named MEK, and has been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma that have a BRAF V600E or V600K mutation. Trametinib has not shown to benefit patients who have already taken another BRAF inhibitor and is only used alone in patients who cannot take vemurafenib or dabrafenib.

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. Mekinist works by blocking the function of the MEK protein, which is overactive inV600E-mutated or V600K-mutated melanoma.
  • 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.

Treatment Side Effects 

 

TAFINLAR (dabrafenib)

Dabrafenib (brand name: Tafinlar) is an oral kinase inhibitor that inhibits another protein, named MEK, and has been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma that have a BRAF V600E or V600K mutation. Trametinib has not shown to benefit patients who have already taken another BRAF inhibitor and is only used alone in patients who cannot take vemurafenib or dabrafenib.

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. Mekinist works by blocking the function of the MEK protein, which is overactive inV600E-mutated or V600K-mutated melanoma
  • 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 

ZELBORAF (vemurafenib)

Vemurafenib (brand name: Zelboraf) is an oral kinase inhibitor that interferes with the action of mutated BRAF and have been approved by 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.

Treatment Side Effects 

Radiation Therapy

Radiation therapy in the adjuvant setting has been shown to improve local control (control melanoma in the lymph node basin) but has not been proven to improve overall survival (keep melanoma from coming back elsewhere in the body) in randomized, controlled studies.

See more information on 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.

See more information on clinical trials

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Stage III Follow Up

It's important to follow up with your melanoma specialist after any procedure. Learn more about the process.

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