Metastatic Melanoma: What to Ask

Advanced melanoma splits into immunotherapy and targeted therapy.

NCI groups three situations together. They are stage III melanoma that cannot be removed, stage IV, and recurrent melanoma. For all three it lists immunotherapy, naming pembrolizumab, nivolumab, ipilimumab, interleukin-2, atezolizumab, and nivolumab with relatlimab. Take that as a catalogue, not a running order. Interleukin-2 is from an earlier era and is now used rarely, in a few centres. What your team proposes rests on your BRAF result, what you have had before, how fast things are moving, and your other health.

The targeted list is dabrafenib, trametinib, vemurafenib, cobimetinib, encorafenib and binimetinib. These are given alone or in pairs.

Which track you can use starts with one test.

Only tumours with the right kind of BRAF change can use the targeted drugs. That usually means a V600 change. The drugs are given in pairs, with a MEK inhibitor. Ask whether BRAF testing was done and which exact variant it found. Then ask whether the drugs are approved for that variant. A positive result does not mean targeted therapy goes first. That depends on how fast things are moving, your symptoms, and what you have had before.

A negative result is not a dead end. It simply means the immunotherapy track is the one available.

Lactate dehydrogenase is a blood test. NCI's melanoma summaries use it as a prognostic marker in advanced disease.

Ask what your level is and how it is being tracked over time.

Melanoma reaches the brain more readily than most cancers, so this comes up early.

NCI describes a trial of nivolumab plus ipilimumab in people with brain metastases. They had no nerve symptoms and needed no urgent treatment. Some had already had focused radiation or surgery for up to three brain spots.

So both radiation and drug treatment have a place. Ask which one your team would do first, and why.

• Has my tumor been tested for a BRAF change?
• If it is BRAF positive, would you start immunotherapy or targeted therapy, and why?
• What is my LDH, and what does the trend mean?
• Have I had brain imaging, even without symptoms?
• If there are brain spots, does radiation come first or does the drug?
• What is the trade-off between one immunotherapy drug and two?
• Which immune side effects mean I should call the same day?

Checkpoint drugs can inflame almost any organ. The usual ones are the bowel, thyroid, liver, lungs, skin and pituitary gland.

Ask for the list in writing and the 24-hour number on the same page, and carry your immunotherapy card. Reporting early matters because the team needs to grade the problem and rule out infection before treating it.

NCI's summaries list isolated limb infusion, and list isolated limb perfusion for unresectable limb melanoma as still under clinical evaluation. They also list talimogene laherparepvec, a treatment injected directly into the deposits.

If your disease is in-transit and limited to one limb, ask whether either applies.

• Call 911 or go to an emergency department if you have a seizure, sudden weakness or numbness on one side, sudden confusion, trouble speaking, or a severe headache that came on fast. Melanoma reaches the brain more often than most cancers, and NCI lists headache, seizures and dizziness as signs of spread there.
• Call 911 or go to an emergency department if you are on a checkpoint drug and chest pain starts, or you are breathless at rest. These drugs can inflame the heart muscle as well as the lungs, and that turns dangerous quickly.
• Call your care team the same day if you are on a checkpoint drug and you get diarrhea several times above your normal, belly pain, a new cough, breathlessness on exertion, yellowing of the skin or eyes, dark urine, or a temperature of 100.4°F (38°C) or higher. These can be the bowel, lung or liver inflammation these drugs cause. Ring the 24-hour oncology line rather than waiting. Say which drug you are on. The team will grade how bad it is and check for infection before they treat it.
• Call your care team within a day or two if you notice a spreading rash, unusual thirst or passing a lot of urine, ankle swelling, or tiredness and dizziness that are new and getting worse. Thyroid, pituitary, kidney and pancreas inflammation build up more slowly, but they still need treating.

Related: Biomarker Testing, Cancer Staging, Clinical Trial vs Standard Treatment, and Palliative Care.

• NCI PDQ — Melanoma Treatment (Patient Version)
• NCI PDQ — Melanoma Treatment (Health Professional Version)
• NCI — Immune Checkpoint Inhibitors
• NCI — Metastatic Cancer