What if metastatic melanoma doesn’t respond to treatment?

In many cases, cancer treatment is not a linear process. Any number of setbacks, side effects, or other circumstances can create a need to adjust treatment plans. This can be especially true when treating an advanced and complex cancer like metastatic melanoma.

Metastatic melanoma is a type of skin cancer that has spread to other areas of the body. Drug resistance and relapses are known challenges, and metastatic melanoma can stop responding to treatments that are initially effective or return after treatment has concluded.

It is critically important to work closely with your cancer care team, who are there to guide you through each step of the treatment process and help you determine when additional steps or a change in direction is needed.

Here, we look at some key questions you and your healthcare team may discuss when deciding on the next steps in a treatment plan for metastatic melanoma.

What treatments have already been used?

Before recommending a next treatment, your healthcare team will review what treatments have already been used, and how the cancer responded to those treatments. Some questions you and your healthcare team may discuss:

• Was there an initial response to treatment?
• Did the cancer stop responding to treatment?
• Did the cancer relapse after treatment?
• Where has the cancer recurred? Has the cancer spread?
• Why and when was the previous treatment stopped? Was it completed, or was it stopped early due to side effects, lack of response, or other circumstances?
• What is your age, overall health, and tolerance for side effects?

Do you need additional testing?

Diagnostic tests help guide treatment, and your healthcare team may order a new set of tests to understand how the cancer is currently behaving. This can include imaging tests to look at the location and size of tumors. It can also include additional lab tests, such as biopsies, which provide a look at how cancer cells are growing and can help decide what treatments the cancer might respond to.

What are the treatment options?

Therapies used when cancer has not responded to an initial therapy are often referred to as second-line therapies. Recommendations are highly dependent on answers to questions like those listed above. Treatment can vary considerably from person to person.

Some examples of cancer treatments used as second-line therapy for metastatic melanoma include:

Targeted Therapy

Targeted therapies attach to specific molecules or “molecular targets” found on cancer cells. This helps these drugs target cancer cells with greater precision than traditional chemotherapy, minimizing damage to healthy cells (though, like any cancer treatment, targeted therapies still cause side effects). In basic terms, these drugs work by blocking proteins that cancer cells require to grow.

Targeted therapy drugs may be used if metastatic melanoma cells test positive for specific gene mutations. The most common examples are BRAF mutations, though there are targeted therapies that work on cancer cells with less common mutations. Drugs called BRAF inhibitors are typically combined with another targeted therapy called MEK inhibitors.

These drugs can be used as a first or second treatment, depending on the circumstances.

Immune checkpoint inhibitors

Immune checkpoint inhibitors are a type of immunotherapy, cancer treatments that work by helping the body’s immune system identify and destroy cancer cells. Some checkpoint inhibitors work by disabling proteins that help cancer cells evade detection by the immune system. Others work by disabling the “off switch” on immune cells, allowing the immune system to attack cancer cells more aggressively.

Immune checkpoint inhibitors are typically used as the initial treatment for advanced melanomas, but some drugs can be used as a second-line treatment in the right circumstances.

Using a combination of checkpoint inhibitors can be more effective against advanced cancers, but carries a greater risk of serious side effects, including severe autoimmune reactions.

TIL therapy

A type of cell therapy called tumor-infiltrating lymphocyte (TIL) therapy can be used as a second-line therapy for select cases of metastatic melanoma. A TIL is a type of immune cell that has entered a cancer cell. While effective at destroying cancer cells, cancer cells replicate at a rate that outpaces the number of TILs in the body.

TIL therapy involves taking a sample of a tumor, extracting TILs from that sample, and multiplying a large number of those TILs in a specialized lab. These TILs are then infused back into the body, where they go to work against cancer cells.

A person will need chemotherapy to prepare for a TIL infusion. They will also need infusions of an immunotherapy called interleukin-2 (IL-2) afterward. This treatment approach requires a hospital stay (1 to 2 weeks). It carries a risk of severe side effects, including very low blood cell counts, the potential for serious infections, and problems with heart, respiratory, and kidney function.

Clinical trials

A clinical trial may offer access to a new therapy or a new combination of therapies. This may be another option you discuss with your healthcare team, who will be your best source of information and can help you understand what clinical trials may be available, what clinical trials you may be qualified for, and how to apply.

Making treatment decisions

Side effects are an important consideration with any of the treatments described above. Potential side effects should always be discussed with a healthcare team before beginning any treatment.

It’s important to remember that metastatic melanoma is a different experience for every person. There is no best approach to treatment, only the treatment approach that works best for a specific person.

Your healthcare team is there to help you understand your diagnosis and treatment options. Healthcare providers will always be your best source of information.