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Stage 4 Melanoma


People with stage 4 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. Significant advances in the treatment of advanced melanoma including the development of precision cancer medicines and immunotherapy have largely replaced chemotherapy and many patients are living for years as a result of these newer treatments.


Newer precision cancer medicines and immunotherapy drugs are the standard of care because they delay the time to cancer recurrence and prolong survival. Patients should discuss the role of genomic testing for determining the best therapy to be used. Systemic therapies commonly used in the treatment of Melanoma include:


BRAF & MEK Kinase Inhibitors


The BRAF and MEK genes are known to play a role in cell growth, and mutations of these genes are common in several types of cancer. Approximately half of all melanomas carry a specific BRAF mutation known as V600E. This mutation produces an abnormal version of the BRAF kinase that stimulates cancer growth. Some melanomas carry another mutation known as V600K. BRAF and MEK inhibitors block the activity of the V600E and V600K mutations respectively. Combinations of a BRAF and a MEK inhibitor appear to decrease the emergence of disease resistance that occurs in patients treated with BRAF inhibition alone.


BRAF inhibitors


• Zelboraf®(vemurafenib) BRAF V600E kinase inhibitor

• Tafinlar®(dabrafenib) BRAF V600E kinase inhibitor

• Braftovi® (enorafenib) BRAF inhibitor


MEK inhibitors


• Mekinist®(trametinib) MEK V600 kinase inhibitor

• Cotellic® (cobimetinib) MEK V600 kinase inhibitor

• Mektovi® (binimetinib) MEK inhibitor




Immunotherapy treatment of melanoma has also progressed considerably and has also become a standard treatment. The immune system is a network of cells, tissues, and biologic substances that defend the body against viruses, bacteria, and cancer. The immune system recognizes cancer cells as foreign and can eliminate them or keep them in check—up to a point. Cancer cells are very good at finding ways to avoid immune destruction, however, so the goal of immunotherapy is to help the immune system eliminate cancer cells by either activating the immune system directly or inhibiting the mechanisms of suppression of the cancer.


Yervoy® (ipilimumab) is a monoclonal antibody that targets CTLA4, found on the surface of T cells. CTLA4 is thought to inhibit immune responses. By targeting this molecule, Yervoy enhances the immune system’s response against tumor cells.


PD-1 “Checkpoint Inhibitors”: Drugs that block the PD-1 pathway can enhance the ability of the immune system to fight cancer and are referred to as checkpoint inhibitors for their ability to help the immune system recognize and attack cancer.  Opdivo (nivolumab) and Keytruda (pembrolizumab) is a checkpoint inhibitors that are approved for treatment of advanced melanoman and are superior to Yervoy.


Proleukin® (interleukine 12) is an immunotherapy agent has traditionally been given in high doses to patients with melanoma, administered either intravenously by rapid infusion or by continuous infusion. Although high doses of Proleukin® historically have been associated with severe side effects management of these has significantly improved over the past decade making this treatment more tolerable.




Although once the standard of care, chemotherapy has largely been replaced by the newer precision cancer medicines and immunotherapies in the management of advanced melanoma. Chemotherapy is still being used in some situations and may represent an appropriate treatment option for selected patients alone or in combination with newer targeted immunotherapies. DTIC (dacarbazine) has been the standard chemotherapy for the treatment of metastatic melanoma, with an overall response rate of approximately 15-20% and no clinical trials directly comparing DTIC to different chemotherapy combinations have demonstrated clear superiority of drug combinations over DTIC alone.


• DTIC (dacarbazine)

• Platinum

• Tamadol (temazolamide)

• Avastin


Clinical Trials:


New anti-cancer therapies continue to be developed and evaluated in clinical trials. There are three phases of clinical trials before approval.  See our clinical trials section for more information.


Managing Liver Metastases


When cervical cancer spreads to the liver, it doesn’t always cause symptoms. It may be picked up by liver function tests, which are blood tests that measure certain levels of enzymes and proteins in the blood. Abnormal levels can indicate liver disease or damage.


If liver metastasis causes symptoms, they can include:


• pain or discomfort in the mid-section

• fatigue and weakness

• weight loss/poor appetite

• fever

• bloating

• swelling in the legs

• a yellow tint to the skin or the whites of the eyes


In addition to liver function tests, doctors use imaging tests to diagnose liver metastases. These may include MRI (magnetic resonance imaging), CT scan (computed tomography), ultrasound, and/or PET scan (positron emission tomography). Sometimes, a combined PET/CT scan is used.


Your doctor also may recommend getting a sample of the suspicious area(s) for examination under a microscope (biopsy). He or she may involve an interventional radiologist to obtain precise and minimally invasive imaging.


The most common treatments for metastatic cervical cancer in any location (bone, brain, lung, or liver) are systemic medications, which treat cancer throughout the entire body. Systemic medications include chemotherapy, targeted therapies, and clinical trials that have already been discussed.  Liver directed therapies, including surgery, may be an option.


Liver Directed Therapies: There are numerous liver directed therapies available for those who are faced with a Stage 4 cervical cancer diagnosis with liver metastases or cervical cancer that has spread to the liver.  These therapies are dependent on the size, number, and location of the liver tumors. These liver directed therapies may include chemoembolization, cryoablation, cyberknife, hepatic arterial infusion, liver resection, proton beam therapy, radioembolization or SIRT, radiofrequency ablation, or SBRT.  You can learn more on our treatment page under liver directed therapies.







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