FDA Approves Adjuvant Ipilimumab to Reduce the Risk of Melanoma Returning After Surgery


The U.S. Food and Drug Administration has expanded the approved use of ipilimumab (Yervoy) to include a new use as adjuvant therapy for patients who have cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm and have undergone complete resection, including total lymphadenectomy.

“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 FDA’s Center for Drug Evaluation and Research. “This new use of the drug in earlier stages of the disease builds on our understanding of the immune system’s interaction with cancer.”

Ipilimumab, administered intravenously, was originally approved in 2011 to treat late-stage melanoma that cannot be removed by surgery. Ipilimumab is a monoclonal antibody that blocks the CTLA-4 molecule, which may play a role in slowing down or turning off the body’s immune system and affects its ability to fight off cancerous cells. Ipilimumab may work by allowing the body’s immune system to recognize, target, and attack cells in melanoma tumors.

Recurrence-Free Survival

The approval was based on improvement in recurrence-free survival in a randomized (1:1) double-blind, placebo-controlled trial in 951 patients with resected stage IIIA (lymph node > 1 mm), IIIB, and IIIC (with no in-transit metastases) histologically confirmed cutaneous melanoma. The study measured recurrence-free survival and overall survival.

Forty-nine percent of participants taking ipilimumab 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 (hazard ratio = 0.75, 95% confidence interval = 0.64–0.90; P < .002, stratified log-rank test). The analysis of overall survival data has not yet been performed.

Adverse Reactions

Safety data were evaluated in 945 patients (median age, 51 years; 65% male), who received ipilimumab at 10 mg/kg (n = 471) or placebo (n = 474) administered as an intravenous infusion for four doses every 3 weeks followed by 10 mg/kg every 12 weeks beginning at week 24 up to a maximum of 3 years. Ipilimumab-treated patients received a median of four doses, and 36% of patients received ipilimumab for longer than 6 months. Ipilimumab was discontinued for adverse reactions in 52% of patients.

The most common side effects of ipilimumab in this study were rash, diarrhea, fatigue, itching, headache, weight loss, and nausea. Grade 3 to 5 immune-mediated adverse reactions occurred in 41% of ipilimumab-treated patients and included enterocolitis (16%), hepatitis (11%), endocrinopathy (8%), dermatitis (4%), and neuropathy (1.7%). The five treatment-related deaths were due to immune-mediated adverse reactions of enterocolitis (3), Guillain-Barré syndrome (1), and myocarditis (1).

Women who are pregnant should not take ipilimumab because it may cause harm to a developing fetus.

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

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.