Adjuvant Immunotherapy in Advanced Melanoma

Source: Cancer Network, April 2018

Cancer Network: First, can you say what is meant by adjuvant therapy for melanoma and describe current FDA-approved immunotherapies available for patients with surgically resected stage III melanoma?
Dr. Weber: The word adjuvant, interestingly, in the English language has many meanings, but the meaning that we use commonly in the clinic is in the sense of ‘added to.’ So, an adjuvant therapy is something that is added to surgery—given after the surgery to decrease the risk that the tumor will return or relapse. In the United States, there are various different adjuvant therapies. For example, for colon cancer we commonly use chemotherapy as adjuvant therapy, and for breast cancer it’s chemotherapy or hormonal therapy. For melanoma, there are actually at least three different approved therapies, all of which are immunologic in nature. The original adjuvant therapy approved by the FDA for melanoma back in the 1990s was high dose alpha-interferon. I should actually say that there are four approved therapies, because a pegylated version of interferon was approved in the last 5 years, again for stage III melanoma at high risk for recurrence. When I say high risk, I usually mean a 50% risk at 5 years or longer of the tumor returning.
Over the last couple of years there have been two new approvals. Back in 2015, the CTLA-4 [cytotoxic T-lymphocyte–associated antigen 4] blocking antibody ipilimumab was approved by the FDA as an adjuvant therapy, and that was given at a pretty high dose of 10 mg/kg. It turned out to be a fairly toxic regimen, although it was the first drug that was shown in a randomized trial, compared to placebo, to actually benefit patients with resected or surgically removed stage III melanoma who clearly had prolonged time to return of the tumor. That is, prolonged relapse-free survival. The patients who received ipilimumab [in clinical trials] also had an increased overall survival.

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