FDA Approves Ipilimumab to Reduce the Risk of Melanoma Recurrence After Surgery

A new use as adjuvant therapy for patients with stage III melanoma

On 28 October 2015, the US Food and Drug Administration (FDA) expanded the approved use of ipilimumab (Yervoy) to include a new use as adjuvant therapy for patients with stage III melanoma, to lower the risk that the melanoma will recur following surgery.

In stage III melanoma, the cancer has spread to one or more lymph nodes. Patients with stage III melanoma are generally treated by surgery to remove the melanoma skin lesions and the nearby lymph nodes.

Yervoy, administered intravenously, was originally approved in 2011 to treat late-stage melanoma that cannot be removed by surgery. Yervoy is a monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4). CTLA-4 may play a role in slowing down or turning off the body’s immune system, and affects its ability to fight off cancerous cells. Yervoy may work by allowing the body’s immune system to recognise, target and attack cells in melanoma tumours.

The safety and effectiveness of Yervoy for this new use were studied in 951 patients who received Yervoy or a placebo as adjuvant therapy following complete surgical removal of melanoma. The study measured recurrence-free survival and overall survival. 

It the study, 49% of participants treated with Yervoy had their cancer return after an average of 26 months, compared to 62% of those receiving a placebo, whose cancer returned after an average of 17 months. The analysis of overall survival data has not yet occurred.

The most common side effects of Yervoy in this study were rash, diarrhoea, fatigue, itching, headache, weight loss and nausea. Yervoy can also cause autoimmune disease in the digestive system, liver, skin, nervous system (which would each require treatment with corticosteroids), as well as in the hormone-producing glands (which requires life-long hormone replacement therapy). Women who are pregnant should not receive Yervoy because it may cause harm to a developing foetus.

Due to the potential for fatal immune-mediated adverse reactions and unusual severe side effects with Yervoy, 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.

Dr Richard Pazdur, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research said: “This new use of the drug in earlier stages of the disease builds on our understanding of the immune system’s interaction with cancer.”

Yervoy is manufactured by Bristol-Myers Squibb in Princeton, New Jersey.