The Best Treatment Options for Metastatic Melanoma

by Erin L. Boyle Health Writer

The new treatments for metastatic melanoma are many things… Like incredible. Revolutionary. Even, as they say in medicine, paradigm-changing. But what does all this mean for you (or a loved one) with an advanced melanoma diagnosis? One very encouraging message: You have a much better chance of surviving this skin cancer type when it’s spread in your body than you would’ve only a decade ago. So close all the tabs in your browser with stories older than 10 years on the topic, and read up on current treatment options for metastatic melanoma here.



Surgery remains the main treatment for early stages of melanoma, but can also be effective in some advanced cases too, says Vadim Gushchin, M.D., a surgical oncologist, and director of The Melanoma and Skin Cancer Center, at Mercy Medical Center in Baltimore. That includes what’s called a lymphadenectomy (when your lymph nodes are removed) in some stage 3 cases. If surgery isn’t the best treatment option, the melanoma might be referred to as unresectable. Be sure to ask your doctor if surgery is a possible treatment, Dr. Gushchin says, because it can have good outcomes.



This exciting—and newer—type of treatment, part of what’s known as systemic therapy, is medication that uses your own immune system to target cancer cells, says Pallavi P. Kumar, M.D., a medical oncologist and director of immuno-oncology at the MedStar Health Cancer Network in Baltimore. Immunotherapy can include infusion medications (checkpoint inhibitors and interleukin-2), viral injections (Talimogene laherparepvec, or T-VEC), a vaccine (the Bacille Calmette-Guerin vaccine), and a cream (Imiquimod). Checkpoint inhibitors and interleukin-2 are particularly well-known.

T-cell cancer

Immunotherapy In-depth: Immune Checkpoint Inhibitors

Among the more recent immunotherapy discoveries in metastatic melanoma treatment are immune checkpoint inhibitors (including PD-1 inhibitors, PD-L1 inhibitor, and CTLA-4 inhibitor). Developed in the late 1990s by researchers in the U.S. and Japan, the first drug approved in this class entered the market in the U.S. in 2011, and was followed by several other drug approvals. Checkpoint inhibitors can have tough side effects, including activating a serious autoimmune response, says Dr. Gushchin. But they can also have stunning results, improving five-year survival rates in patients with metastatic melanoma by nearly 10 times the previous rates.


Immunotherapy In-depth: Interleukin-2

Another form of immunotherapy, interleukin-2 (IL-2) can help shrink advanced melanomas, which is especially helpful when other treatments aren’t working. This medication isn’t used now as much as it was before immune checkpoint inhibitors entered the market because of its extensive side effects. These include flu-like symptoms of fever, chills, aches, fatigue, and low blood counts, according to the American Cancer Society.


Targeted Therapy for Metastatic Melanoma

In 2002, a scientist discovered a mutation found in about half of all melanoma cases. “Molecular profiling of tumors can find targets that may be useful,” Dr. Kumar explains. “In melanoma, there is one such target known as BRAF. We can test the tumor to see if it has this mutation. If the mutation is present, there are medications that can be used to shrink the tumor down.” Those targeted therapy medications, called BRAF inhibitors, were first approved in 2011. When used in combination with MEK inhibitors, they have good response rates. These drugs do have side effects, including rashes, itching, and fever.

daily pill box

Combination Therapy for Metastatic Melanoma

Many of these newer immunotherapy and targeted therapy drugs, when used in combination, can have excellent, improved results, even better than when used alone. Two drugs in the same class can also have the same intensifying effect. For instance, researchers published a study in The New England Journal of Medicine in 2019 showing how combining two immune checkpoint inhibitors had overall survival at five years of 52%, as opposed to 44% and 26%, respectively, when used alone.

cancer patient and doctor

Adjuvant Therapy for Metastatic Melanoma

This therapy type is typically given as secondary treatment after the first, or primary treatment (often surgery), to help reduce the risk of cancer recurring. One of the first drugs of this type was approved around 2011. “We are realizing using these immunotherapy and targeted therapies may prolong the time that patient is without disease. We are hopeful with continued learning, understanding, and clinical trial work, this will translate to survival benefit,” Dr. Kumar says of adjuvant therapy, which has had excellent results.

radiation therapy

Radiation Therapy, Chemotherapy to Treat Metastatic Melanoma

Older treatments like radiation therapy (RT) are still used to treat melanoma, but some older treatments are being overshadowed by the newer, more dazzling therapeutic options, especially for advanced disease, Dr. Gushchin says. RT is typically used in patients who can’t have surgery or to relieve symptoms. Chemotherapy is used even less these days because of how wildly successful immunotherapy, targeted therapy, and adjuvant therapy have been for this cancer type when it advances.

clinical trial

Participating in a Clinical Trial for Metastatic Melanoma

Even with all of these new treatments, more are being researched—which is why you may want to take part in a clinical trial, if you’re eligible, to help researchers discover additional ways to increase survival and quality of life with metastatic melanoma. One place to look for clinical studies: Clinical Dr. Kumar encourages those with advanced melanoma to discuss clinical trials with their doctor. “Knowledge can change the future for so many because of clinical trials,” he says. “Patients are not only trying to find what can work for them, but helping others in the future have a chance.”

Erin L. Boyle
Meet Our Writer
Erin L. Boyle

Erin L. Boyle, the senior editor at HealthCentral from 2016-2018, is an award-winning freelance medical writer and editor with more than 15 years’ experience. She’s traveled the world for a decade to bring the latest in medical research to doctors. Health writing is also personal for her: she has several autoimmune diseases and migraines with aura, which she writes about for HealthCentral. Learn more about her at Follow her on Twitter @ErinLBoyle.