The US 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.
Ipilimumab, a monoclonal antibody that blocks CTLA-4, was first approved in 2011 to treat late-stage melanoma in patients who are not candidates for surgery.
"Today's approval of ipilimumab extends its use to patients who are at high risk of developing recurrence of melanoma after surgery," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, in a statement. "This new use of the drug in earlier stages of the disease builds on our understanding of the immune system's interaction with cancer."
"Today's approval marks the first new FDA approved adjuvant option in 20 years," said Tim Turnham, PhD, executive director, Melanoma Research Foundation, in a statement. He notes that previous options for stage III patients have been interferon or close observation. "This approval means Stage III melanoma patients have a powerful new tool to help prevent their disease from progressing."
The safety and effectiveness of Yervoy as adjuvant therapy 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.
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%).
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. The analysis of overall survival data has not yet occurred.
The most common side effects reported in this study 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.
The results of the EORTC 18071 study were published May 15 in Lancet Oncology, and the authors of the study noted that the "adverse event profile was consistent with that observed in advanced melanoma, but at higher incidences in particular for endocrinopathies. The risk–benefit ratio of adjuvant ipilimumab at this dose and schedule requires additional assessment based on distant metastasis-free survival and overall survival endpoints to define its definitive value."
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 will also be provided to patients to inform them about the therapy's potential side effects.
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Cite this: Roxanne Nelson. FDA Approves Ipilimumab (Yervoy ) for Use in Stage III Melanoma - Medscape - Oct 28, 2015.