Combination Therapy for Metastatic Melanoma

Medically Reviewed by Melinda Ratini, DO, MS on August 26, 2020

When you have melanoma (a form of skin cancer) that has spread to other parts of your body (which is called metastatic cancer or stage IV cancer), your doctor may tell you that you need combination therapy. This means you’ll get more than one treatment at the same time to attack the cancer cells.

Years ago, the main weapons that doctors used to fight cancer were surgery, chemotherapy (strong medicine that kills healthy cells along with cancer cells), and radiation. Today, there are many new tools, like immunotherapy, which boosts your body’s own immune system to help it fight cancer, and targeted therapy, which targets and attacks certain mutated genes or proteins that are in some forms of cancer without harming normal cells.

Often, when doctors combine two or more ways to fight cancer, they have a greater result than when they use only one cancer-fighting weapon at a time. This type of treatment lets them attack cancer from many angles at the same time, so there are fewer places for it to hide. This makes it more likely that the treatments will help.

Your doctor will decide what type is best for you based on your health and the type of melanoma you have. They’ll also choose the best option to try first. Some treatments may never be right for you, if your form of melanoma doesn’t have certain mutated genes or proteins.

You may have more severe side effects than if you only got one treatment at a time. Your doctor may choose to stop one if the side effects are too severe. They may also stop a treatment if you don’t improve by a certain time.

Your doctor may suggest these combinations:

Immunotherapy Drugs

Research has shown that using two drugs to treat stage IV melanoma works better than using just one. Cancer can trick your immune system into leaving it alone. These meds “wake up” your body so you can fight back.

When ipilimumab (Yervoy) is paired with either nivolumab (Opdivo) or pembrolizumab (Keytruda) survival rates are better than treating with ipilimumab alone.

Your doctor will know whether or not this drug combo is right for you. You could be more likely to have a serious heart problem or other severe side effects than if you only took one of the drugs.

Targeted Therapy Drugs

Some of today’s newer cancer treatments target certain mutated genes or proteins that cancer needs to thrive or survive. If your melanoma has them, you can take a medication to attack them.

About half the people with melanoma have a change to their genes called BRAF. Other people have a certain protein called MEK that helps melanoma grow and thrive. If your cancer has them, the doctor may give you a mix of binimetinib (Mektovi) and encorafenib (Braftovi), dabrafenib (Tafinlar) and trametinib (Mekinist) or two other drugs called cobimetinib (Cotellic) and vemurafenib (Zelboraf). They can shrink tumors and help you live longer. But there can be strong side effects.

Chemotherapy Drugs

Chemotherapy isn’t the first treatment choice for melanoma. But some patients with stage IV melanoma do get chemo drugs as a type of combination therapy. There are a number of drugs that your doctor can choose from, and it’s likely that you’ll receive more than one such drug at a time. This mix works well to shrink tumors, but it may also cause more side effects.

Upcoming Options

Doctors are testing other forms of combination therapy for melanoma in clinical trials. Several treatments look like they may have promise. Ask your doctor if a clinical trial is right for you.

These treatments may be available outside of clinical trials if they prove to be worthy:

  • A combination of immunotherapy drugs for people who have less-advanced melanoma
  • A combination of immunotherapy and targeted therapy for people with stage IV melanoma
  • A combination of immunotherapy and radiation (which is called radioimmunotherapy) for people with melanoma. Right now, doctors use it to treat certain types of lymphoma, which is another form of cancer.
  • A combination of immunotherapy and a cancer-fighting vaccine for people with melanoma


WebMD Medical Reference



American Society of Clinical Oncology: “Melanoma: Treatment options.”

American Cancer Society: “Evolution of cancer treatments: Chemotherapy,” “What’s new in melanoma skin cancer research?”

Karmanos Cancer Institute: “Frequently asked questions.”

Melanoma Research Foundation: “Melanoma Treatment.”

Nemours Foundation: “Chemotherapy.”

National Cancer Institute: “Targeted Cancer Therapies,” “Pembrolizumab Improves Overall Survival in Patients with Advanced Melanoma.”

Medscape: “Malignant Melanoma Treatment & Management.”

Radiological Society of North America: “Radioimmunotherapy (RIT).”

Cancer Research Institute: “Melanoma.”

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