Melanoma Adjuvant Therapy Is Refined and Improved Through Ongoing Research

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Adjuvant therapy: a new frontier for treating melanoma

Adjuvant therapies for melanoma have been rapidly advancing, offering patients more treatment options where few alternatives existed just a few years ago. Researchers like Douglas Johnson, M.D., a medical oncologist at Vanderbilt University Medical Center who specializes in melanoma treatment and research, are working to find ways to improve adjuvant therapies for melanoma. Dr. Johnson spoke with HealthCentral by phone.


Adjuvant therapy’s goal is to prevent melanoma recurrence

A patient receives adjuvant therapy for melanoma after main treatment, usually surgery to remove the tumor, to prevent a recurrence of the disease. Patients don’t have any active disease while going through this treatment. Adjuvant therapy may be beneficial to patients with stage 3 or stage 4 melanoma because they are at higher risk of a recurrence.


Why do some patients respond better than others to adjuvant therapies?

One major challenge that researchers face is predicting how patients will respond to cancer therapies, including adjuvant therapies. Johnson is among those who are working to better understand how individuals’ immune systems play a role in determining how a patient responds to adjuvant treatment. He’s also looking at how the specific characteristics and mutations of a patient’s tumor may be a consideration when choosing the right adjuvant therapy.


Adjuvant therapies may come with potentially severe side effects

The FDA has approved the use of immunotherapies (also called checkpoint inhibitors) and targeted therapies to be used in adjuvant treatment. One major concern is that some new adjuvant therapies may have rare, but sometimes severe and even fatal, side effects. However, these therapies have also allowed many melanoma patients to live without cancer recurrence, Johnson noted.


Researchers study genetic factors that may make side effects more likely

Researchers are looking at ways to predict who might have severe side effects from immunotherapy. They’re studying if there are genetic factors or gene variants that predispose people to certain side effects. “Are there antibodies that we could detect in the blood that would predispose patients to side effects, or are there genetic factors in the tumor that predispose patients to side effects and create cross-reactivity?” Johnson said.


Could “good” gut bacteria help make treatment more successful?

Another line of research is looking into the role that a patient’s gut microbiome, or gut bacteria, might play in how well patients respond to treatment. Some researchers are studying if “good” bacteria in a patient’s microbiome may help reinforce the immune system so it can do its job better and also help patients avoid some side effects. “Right now, it’s a bit of a black box,” Johnson said. “We really don’t have a good handle on why some patients have side effects.”


Patients with BRAF mutation respond well to targeted therapy

About half of melanoma patients have a BRAF mutation in their tumor cells which triggers the cancer cells to develop abnormally and divide out of control. “People who have the BRAF mutation are especially responsive to the targeted therapy,” Johnson said. Targeted therapy drugs (also known as BRAF inhibitors) work by blocking the activity of the MEK protein or the mutated BRAF protein.


Why do some patients become resistant to targeted therapy?

Targeted therapies have fewer serious side effects than immunotherapies and they’re effective at keeping cancer from recurring for nearly all metastatic melanoma patients. However, the results aren’t always long-lasting, Johnson said. For some patients, these drugs stop being effective after about a year, and then the cancer returns.


Some patients may opt for additional testing to see if targeted therapy is an option

“Right now, we don’t know which therapy is superior for adjuvant treatment, targeted therapies or immunotherapies,” Johnson said. But knowing your treatment options are the first step. If you have stage 3 or higher melanoma, Johnson recommends you have genetic testing done on the tumor to see if it has the BRAF mutation. This will give doctors more information when deciding what treatment options and adjuvant treatment options are available to you.


Researchers are studying other gene mutations and how to best treat them

There are other gene mutations that can also play an important role in melanoma, Johnson said. These include mutations to the C-KIT and NRAS genes, which also contribute to causing melanoma tumors to grow out of control. A smaller number of patients with melanoma have these mutations, so not all patients may choose to undergo testing for them, Johnson said.


Melanoma tumor’s “total mutation burden” also plays a role

Researchers are also beginning to understand the importance of looking at the total mutation burden, or mutation load, of a melanoma tumor. The more mutations a tumor has, the more likely it is to have the right mutation needed for the immune system to recognize cancer cells, Johnson said.


The immune system can better recognize tumors that have more mutations

Knowing if a patient has had melanoma with a high mutation burden can also help determine which adjuvant therapy he or she is best suited for, Johnson said. Tumors with a higher amount of mutations in its genes may respond well to immunotherapies, Johnson noted. “A number of studies have found that the more mutations a tumor has, the more foreign it will appear to the immune system, so the more likely the cancer will respond to immunotherapy.”


Neoadjuvant therapy: the new frontier to treating patients before surgery

Researchers are also looking at the benefits of neoadjuvant therapy in treating melanoma. Neoadjuvant therapy is treatment given to shrink a tumor before surgery. Clinical trials are underway to look at using new therapies in a neoadjuvant setting, and if this would ultimately help decrease rates of recurrence.  “So that’s a potential new frontier,” Johnson said.