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How is Melanoma Treated After Surgery? The Landscape of Therapies Explained

Julie Ryan Evans

Treating Melanoma After Surgery

  • After melanoma is surgically treated, sometimes additional therapy is given, known as adjuvant therapy.
  • Adjuvant therapy helps to kill any remaining cancer cells, and helps to reduce the risk of the cancer coming back.
  • Common adjuvant therapies for melanoma include immunotherapy such as pembrolizumab or nivolumab or targeted therapy such as dabrafenib and trametinib.
 

One of the most common and effective ways to treat melanoma is with surgery. And for some early stage cases, that’s enough.  In other cases, however, additional therapy after surgery is recommended to help improve the outcome and reduce the risk of recurrence.

Types of Adjuvant Therapy

Adjuvant therapy refers to those treatments administered after surgery designed to improve outcomes and decrease the risk of recurrence. Those the FDA has approved for melanoma include:

  • Pembrolizumab (Keytruda) – This medication is an immunotherapy that helps your immune system attack and kill cancer cells. It is a PD1 inhibitor drug that works by blocking the PD1 pathway used by cancer cells to hide from the immune system.
  • Nivolumab (Opdivo) – Another form of immunotherapy, nivolumab is also a PD1 inhibitor that works similarly to pembrolizumab.
  • Dabrafenib (Tafinlar) and trametinib (Mekinist) combination – This is a targeted therapy combo for patients with a BRAF V600E/K mutation fueling their cancer. About 50% of melanomas have BRAF mutations.
  • Ipilimumab (Yervoy) – This medication is also an immunotherapy. Ipilimumab blocks the activity of a molecule called CTLA-4, a protein that prevents your immune system’s T cells from attacking your normal body cells and cancer cells.
  • Interferon alpha (FDA-approved, but no longer recommended by the National Comprehensive Cancer Network (NCCN) Melanoma Panel.)

According to the NCCN guidelines, adjuvant treatment outside of a clinical trial is not recommended for patients with stage I disease.

In 2021, the FDA approved pembrolizumab (Keytruda) for treatment of patients with Stage IIB or IIC melanoma after surgery. NCCN guidelines were updated to reflect this approval and add this option as a recommendation.

NCCN guidelines recommend adjuvant treatment with immunotherapy or targeted therapy for some stage III and stage IV disease that can be primarily treated with surgery.

Dr. Cecilia Larocca, a dermatologist at the Dana-Farber Cancer Institute says immunotherapy has helped changed the landscape of melanoma treatment.

“When immunotherapy came on the market it was such an exciting time for everyone involved in the care of melanoma, the main reason being is it went from this scary, unmanageable cancer with no treatments to one that could potentially have an incredibly long-lasting result with patients absolutely never having to worry about their melanoma, aside from having us do regular skin checks,” Dr. Larocca said in a previous conversation.

Targeted therapy is also making an impact.

“So when it comes to melanoma and targeted therapy, one of the main things that your oncologist will do is evaluate whether or not it has a particular mutation called BRAF. If your cancer has a BRAF mutation, there is a particular target therapy that you might be available to use,” Dr. Larocca said. “This combination therapy is now working its way earlier into the treatment paradigm for melanoma, both in the adjuvant setting – meaning treating patients who are at high risk for recurrence but don’t actively have cancer – as well as treating patients who actively have metastatic disease.”

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Deciding On Additional Therapy

The decision to undergo adjuvant therapy should be made with your doctor taking into consideration the follow items, according to the NCCN:

  • Risk of recurrence
  • Potential clinical benefit
  • Potential toxicities
  • Patient preference
  • Patient age
  • Comorbidities (other health issues such as heart failure, kidney disease)

The patient should have a detailed conversation with their medical team to discuss the pros and cons for additional therapy.

The Future Of Adjuvant Therapy

Promising adjuvant treatments for melanoma are on the horizon, too. Clinical trials underway include:

  • Bempegaldesleukin (NKTR-214) and nivolumab (Opdivo): Several ongoing trials are evaluating the combination of bempegaldesleukin and nivolumab for adjuvant therapy of melanoma, versus nivolumab alone.

These studies haven’t matured, so it may be three or more years before official results are in, but experts are hopeful.

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“We’re part of that study. It’s a good study,” says Dr. Jeffrey Weber, an oncologist and melanoma specialist at NYU Langone’s Perlmutter Cancer Center. “It’s a well-powered, thousand-patient randomized study. And in a couple of years, or maybe three years when it matures, we’ll know whether the combo is better than just (nivolumab), as adjuvant therapy.”

Dr. Weber points to a phase II study of patients with previously untreated stage III/IV melanoma testing the combo of bempegaldesleukinand nivolumab. “It had a 30 percent rate of complete responses, which is unheard of,”  says Dr. Weber. “There’s almost no therapy that gives you a 30 percent complete response rate in any sphere of melanoma. So, that looked pretty promising.”

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Cautions About Adjuvant Therapies

Dr. Webber says one concern when it comes to adjuvant therapies, however, is the potential for overtreatment of patients.

“This is a big issue,” he said. “Do you treat adjuvantly and overtreat half the patients? And treat four patients to benefit one or five, to benefit one? Or do you wait and only treat the half of patients who need it? And allow two-thirds of them to progress and presumably die of melanoma? I’ve always been trained to be aggressive. I admit that it’s an expensive proposition to treat every patient with adjuvant NIVO for a year. ”

He says cost is a major concern as well.

RELATED: The Future of Biomarkers in Melanoma Treatment

“Bottom line is, pharmacoeconomics is a big deal,” Dr. Weber said. “You can’t ignore it. There is only so much money. This is a very rich country, by the way. But even this country has only so much money. So the more drugs you put together, the higher the charges. Eventually, we’re going to run out of money and we’re going to have to ration. Unfortunately, I couldn’t condone rationing the use of PD-1 antibodies by not treating people in the adjuvant mode when they’re at a high enough risk. We desperately need biomarkers to predict who’s going to relapse.”

Questions to Ask Your Doctor

  • Is additional treatment needed after I have surgery to treat my melanoma?
  • How soon can I start treatment after surgery?
  • Which treatment options do I have after surgery?
  • Is there one treatment option that is more beneficial for me?
  • What are the side effects?
  • How will we know if this treatment is working for me?
  • Should I get a second opinion?

Preventing Melanoma

The biggest tool against melanoma and other skin cancers is prevention. ​​In a previous interview with SurvivorNet, Dr. Dendy Engelman from MDCS Dermatology in New York shared the top five things you can do to avoid skin cancer:

  • Avoid sun during peak hours, which is 10 a.m. to 2 p.m.
  • Wear a wide brimmed hat and sunglasses to protect the tops of our heads, the tops of our ears and the delicate area around the eye.
  • Wear at least SPF 30 sunscreen and make sure to reapply every two hours or after excessive sweating or swimming.
  • Have yearly skin checks (with a professional), because it’s difficult to evaluate areas all over the body.
  • Avoid tanning beds. There are no “good” tanning beds, and they can significantly increase your risk of melanoma.

Dr. Dendy Engelman from MDCS Dermatology in New York talks about why it’s important to protect your skin all year long.

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