Breakthroughs in Treating Advanced Melanoma

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Melanoma treatment is very successful when doctors find the cancer before it starts growing in other areas of the body. Advanced melanoma that has spread—or metastasized—is harder to treat. For many years, surgery, X-ray treatment, and drugs that kill cancer cells were the only treatments available for advanced melanoma. None of them worked very well.

Immunotherapy (using injectable drugs like pembrolizumab, nivolumab, and ipilimumab) was a breakthrough treatment in years past. Immunotherapy stimulates the immune system to fight cancer cells. This treatment proved to be more effective than mainstay cancer treatments.

Today, immunotherapy, including combination therapy with both ipilimumab (Yervoy) and nivolumab (Opdivo), are standard treatment for metastatic melanoma. But the breakthroughs haven’t stopped. The newest treatment option for advanced melanoma is targeted therapy.

What Is Targeted Therapy?

Researchers found that some people with melanoma have abnormal genes that trigger the growth of melanoma cancer cells. In fact, about half of all melanomas show a gene mutation that causes the tumor to grow. These genes include BRAF, MEK and C-KIT.

Doctors can now do a special type of biopsy to tell whether an abnormal gene is causing a melanoma tumor to grow. If your melanoma has these mutations, there are new drugs that target them. The U.S. Food and Drug Administration (FDA) approved these drugs as treatment for advanced melanoma. The drugs block the abnormal proteins from these genes and stop the tumor from growing. It's important to note, they are used only for melanomas that cannot be removed by surgery.

Targeted Therapy Drugs

Targeted therapy drugs have a big advantage over chemotherapy and radiation therapy because they target only cancer cells. Chemo and radiation kill normal cells along with cancer cells. Targeted therapy drugs don’t generate the familiar chemo and radiation side effects because they generally spare normal cells. These drugs have a different risk profile and may make you vulnerable to serious infections and increase your risk for other types of cancer. Be sure you understand all of the potential risks before consenting to treatment.

Current targeted therapy drug options include:

BRAF Inhibitors

About half of melanoma tumors have a defective BRAF gene. BRAF inhibitors target a protein the abnormal gene makes that helps the tumor grow. BRAF inhibitors for advanced melanoma include:

  • Vemurafenib (Zelboraf). The FDA approved this drug for targeted therapy in 2011. It is approved for people who are positive for the BRAF gene mutation. Several studies show that it helps extend survival. Vemurafenib is a pill you take twice a day. Possible side effects include fatigue, rash, sun sensitivity, and an increased risk of other types of skin cancers.
  • Dabrafenib (Taflinar). The FDA approved this drug in 2013. You take this drug as a capsule twice a day. It appears to be as effective as vemurafenib. Side effects can include flu-like symptoms and thickening of the skin. It is less likely than vemurafenib to cause other skin cancers.
  • Encorafenib (Braftovi). This drug gained FDA approval in 2018. It is for use in combination with binimetinib—a member of the MEK inhibitor class of targeted therapies. The combination showed greater effectiveness and less serious side effects than either drug alone. You take this drug by mouth once a day.

MEK Inhibitors

MEK genes make a protein that is related to the BRAF protein. Some melanoma cells contain a mutated MEK gene in addition to the BRAF mutation. The genes basically work together to help the tumor grow. So, people with abnormal BRAF and MEK genes may also benefit from taking MEK inhibitors. MEK inhibitors for melanoma include:

  • Trametinib (Mekinist). The FDA approved this drug in 2013. You take this pill once a day. It may work best in combination with a BRAF inhibitor. Side effects include rash and diarrhea. Heart, lung and vision problems are rare but serious possible complications.
  • Cobimetinib (Cotellic). The FDA approved this drug in 2015. You take this pill once a day in combination with Zelboraf. Side effects include skin photosensitivity, decreased heart function, metabolic imbalances, and vision problems.
  • Binimetinib (Mektovi). FDA approval for this drug came in 2018, in combination with Braftovi. It’s a twice daily medicine. The most common side effects from the combination include fatigue, nausea, vomiting, diarrhea, abdominal pain, and joint pain or swelling.

C-KIT Drugs

Changes in C-KIT genes aren’t as common as BRAF and MEK abnormalities. Still, some melanomas depend on this defective gene to grow. If testing reveals changes in C-KIT, doctors may recommend imatinib (Gleevec) or nilotinib (Tasigna).

What the Future Holds

There's still a lot to learn about the best ways to use targeted therapies for advanced melanoma. It’s likely that researchers will discover more genes to target and develop new drugs to use in different combinations.

Scientists also continue to investigate new approaches to immunotherapies. This includes a potential melanoma vaccine that uses bits of a melanoma cell to stimulate the immune system. TILs (tumor-infiltrating lymphocytes) are another active area of research. Scientists are testing ways to make TILs—special immune system cells—more effective at fighting melanoma. In short, the future continues to evolve for advanced melanoma treatments.

Talk with your doctor about the best options for you. If you have advanced melanoma, a clinical trial might be the best place to get access to a new treatment. Medications may be free, and you will get to work with doctors on the cutting edge of melanoma research. You may not only benefit from a breakthrough treatment, but you could also be a part of developing new treatments for others who follow.

Key Takeaways

  • New genes and medicines for advanced melanoma are being actively investigated.
  • Researchers discovered abnormal genes that encourage melanoma growth.
  • Medications that attack these specific genes and slow down growth are now available.
  • A clinical trial can be a good option for possibly receiving the latest advanced melanoma treatment.
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Medical Reviewer: William C. Lloyd III, MD, FACS
Last Review Date: 2021 Feb 23
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