FDA Expands Approval for Ipilimumab to Treat Melanoma

The Food and Drug Administration (FDA) expanded the approved use of ipilimumab (Yervoy, Bristol-Myers Squibb) so that it will include a new indication as adjuvant therapy for patients with stage III melanoma. The approval is big news, because it’s the first new FDA-approved adjuvant option for late-stage melanoma in two decades. The only previous treatment option for stage III melanoma patients was interferon.

Ipilimumab, a monoclonal antibody, blocks cytotoxic T-lymphocyte-associated protein (CTL-4), a protein receptor that downregulates the immune system in patients with melanoma and other types of cancer. It was first approved in 2011 to treat late-stage melanoma in patients who are not candidates for surgery.

In a statement about the approval, Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said, “Today’s approval of ipilimumab extends its use to patients who are at high risk of developing recurrence of melanoma after surgery. “This new use of the drug in earlier stages of the disease builds on our understanding of the immune system’s interaction with cancer.”

The approval is based on results from EORTC 18071, a randomized, double blind trial that was conducted in 951 high-risk patients with stage III melanoma who had undergone a complete lymph-node dissection. (See study abstract from Lancet Oncology here.) At 26 months, recurrence-free survival was significantly higher in the ipilimumab group compared with the placebo group, at 1 year (63.5% vs 56.1%), at 2 years (51.5% vs. 43.8%), and at 3 years (46.5% vs. 34.8%).

That response is not only significant, but it also proved durable. Patients in the ipilimumab group were 25% less likely to experience melanoma recurrence than those in the placebo group (hazard ratio, 0.75; 95% confidence interval, 0.64 - 0.90; P = .0013). Median recurrence-free survival was also better in the ipilimumab group (26.1 vs. 17.1 months).

A total of 49% of participants taking ipilimumab had a recurrence after an average of 26 months compared with 62% percent of those receiving a placebo. Overall survival data will not be available until further research is conducted.

The most common side effects reported in EORTC 18071 were rash, diarrhea, fatigue, itching, headache, weight loss, and nausea. Adverse events led to discontinuation of treatment in 245 (52%) of 471 patients who started ipilimumab, including 182 [39%] during the initial treatment period of four doses.

In addition, five patients (1%) died due to drug-related adverse events (AEs). That AE profile was consistent with that observed in advanced melanoma, although the researchers cautioned that there was a higher incidence of AEs higher incidences for endocrinopathies.”

The drug is contraindicated in pregnancy. Due to the potential for fatal immune-mediated adverse reactions and unusual severe side effects, the label includes a Boxed Warning. A Medication Guide for patients will also be provided and will include detailed information on potential side effects.