Not-So-Routine Maintenance: Treating Melanoma After Surgery

Before melanoma spreads past the lesion on the skin, doctors can usually remove the tumor and get rid of the cancer. But people who have stage 2B, 2C or stage 3 melanoma have a greater than 30 percent chance of developing melanoma again. “For these patients, we recommend adjuvant treatment after recovery from the initial surgery to reduce this risk,” says Ahmad Tarhini, a professor in the division of hematology/oncology at University of Pittsburgh. This is known as maintenance therapy.

• Interferon is approved by the U.S. Food and Drug Administration (FDA) to lower the risk of melanoma recurrence. Usually, people receive the drug intravenously five days per week for four weeks. Then they inject it on their own three days per week for 48 weeks. Studies have shown that the drug can help people live relapse-free for longer. But not all studies have shown that the drug extends overall survival time. The side effects — which can include flu-like symptoms, depression and possibly lifethreatening heart and liver damage — can be so severe that some experts question the net benefits.
• Yervoy (ipilimumab) helps people with metastatic melanoma by boosting the immune system’s response. The immune system has so-called checkpoints that prevent the body from attacking every non-threatening substance it comes into contact with. If not for these checkpoints, the body might break out in a rash or fever in response to every unknown particle. However, cancer cells can sneak through these checkpoints unseen. When patients receive Yervoy intravenously every three weeks for 12 weeks, it can block the CTLA-4 checkpoint and slow or stop the progress of cancer. Current clinical trials are examining whether this drug could prevent melanoma recurrence, too. Because the drug alters the function of the immune system, it can cause severe inflammation of organs, skin, nerves, glands and eyes. These side effects can be life-threatening.
• About half of people with melanoma have a mutation in the BRAF gene. Zelboraf (vemurafenib), Tafinlar (dabrafenib) and Mekinist (trametinib) can extend their lives when they have metastatic disease. However, people tend to develop a resistance to the drugs in less than a year. These drugs can cause side effects including carcinomas, other severe skin inflammations and eye inflammation. Each individual drug may bring other side effects. People who develop carcinomas while taking these drugs can have the lesions removed without stopping treatment. Current clinical trials are exploring whether these drugs can prevent recurrence of melanoma in people with BRAF mutations who have non-metastatic disease.
• Keytruda (pembrolizumab), like Yervoy, is an immunotherapy. It helps to extend survival by blocking the protein PD-1, which would otherwise inhibit the immune system from attacking cancer. The drug is indicated for patients with melanoma that is not treatable with surgery or that has spread, and that has progressed after treatment with Yervoy and with a BRAF inhibitor, if the cancer is BRAF-positive. It is given intravenously every three weeks until disease progression or unacceptable toxicity, and side effects can include fatigue, nausea, cough, itching and immune-related problems such as pneumonitis, colitis or hepatitis. The FDA has granted priority review to Keytruda as a potential first-line treatment for advanced melanoma, and expects to make a decision at the end of this year. Meanwhile, clinical trials are investigating whether Keytruda may be able to help keep later-stage melanoma from progressing after surgery.
• Opdivo (nivolumab) is yet another PD-1-inhibiting immunotherapy, appropriate for the same patients who are eligible for Keytruda. Opdivo, which has demonstrated an ability to prolong survival in patients with advanced melanoma, is given intravenously every two weeks until disease progression or unacceptable toxicity, with side effects that can include rash, cough, itching, infection of the upper respiratory tract, swelling of the extremities and immune-related symptoms such as pneumonitis, colitis or hepatitis. Opdivo has received priority review from the FDA as a potential first-line treatment for unresectable or metastatic melanoma. And, like Keytruda, it is being studied in the clinic for its potential to keep advanced melanoma from growing after surgery.