FDA Approves Immunotherapy to Help Prevent Relapse of Melanoma

As of Wednesday, patients with operable stage III melanoma can now receive the immunotherapy drug ipilimumab (Yervoy®) as adjuvant therapy to help prevent recurrence of their cancer. The FDA based its approval on the results of a phase III trial which showed that ipilimumab reduced the risk of recurrence by roughly 25% compared to placebo.

Melanoma is classified as stage III when it has reached one or more lymph nodes. Patients are usually treated with surgery to remove the primary tumors and nearby lymph nodes, but there is a high risk of recurrence (about 60%). Adjuvant therapies—therapies to prevent recurrence—are badly needed. Currently, only one adjuvant therapy is approved in the U.S.—interferon-alpha. Studies have shown that interferon-alpha reduces the risk of recurrence by about 14%, but the treatment is reported to be a very unpleasant one by patients who have received it.

Ipilimumab is an immunotherapy drug known as a checkpoint inhibitor, which “takes the brakes off” the immune system, allowing it to mount a stronger attack against cancer. It was first approved, in 2011, for the treatment of metastatic melanoma, at a dose of 3mg/kg. The dose approved for adjuvant therapy is 10mg/kg.

The potential benefits of adjuvant ipilimumab (ipi) were tested in a study of 951 patients who received either ipi or a placebo following surgery. The study measured the amount of time after treatment it took for the cancer to come back. About 50% of patients taking ipi had their cancer return after an average of 26 months, compared to 62% of patients receiving a placebo whose cancer returned after an average of 17 months. In other words, patients receiving ipi experienced, on average, fewer recurrences and longer recurrence-free survival than patients receiving surgery alone.

Like other immunotherapies, ipilimumab has the potential to cause significant immune-related side effects, some of which can be fatal. In the phase III trial, ipilimumab was discontinued for adverse reactions in 52% of patients.

Because the adjuvant dose of ipilimumab is higher than the dose used for the treatment of metastatic melanoma, the cost is higher as well—about three times as much. To help ensure patient access, Bristol-Myers Squibb, the maker of the drug, has a program to make the drug available to eligible patients at no cost.

This is the fifth immunotherapy regimen approved by the FDA this month, and the third for melanoma. Earlier in the month, the FDA approved the combination of ipilimumab and nivolumab for the treatment of advanced melanoma, and just this week it approved the oncolytic virus therapy T-VEC for the treatment of melanoma that has recurred following surgery.

Melanoma is the deadliest form of skin cancer. In 2015, in the U.S., approximately 73,870 new melanomas will be diagnosed, and about 9,940 people will die from this disease. The incidence of melanoma is also on the rise in the U.S. and around the globe. Immunotherapy represents a new and very promising way to treat—and possibly cure—this deadly disease.