Applying its priority review route, the FDA approved the biologic medication ipilimumab (Yervoy; Bristol-Myers Squibb) as a second-line therapy for the treatment of patients with unresectable or metastatic melanoma. Ipilimumab is the first drug that has shown improved overall survival (OS) in late-stage disease, and is the first drug approved for this patient population in the past 13 years.
This new targeted therapy represents a new class of drug, known as a targeted T-cell antibody. It works by blocking cytotoxic T-lymphocyte–associated antigen 4, which enhances antitumor T-cell response.
In 2010, an estimated 68,130 new cases of melanoma were diagnosed in the United States, resulting in approximately 8700 deaths, according to the National Cancer Institute. Late-stage melanoma has very few treatment options, and none has so far shown improved OS.
Ipilimumab “is the first therapy approved by the FDA to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment,” said Richard Pazdur, MD, Director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research.
The pivotal study (study 020) was conducted in previously treated unresectable patients with stage III or stage IV melanoma. Patients receiving the combination of ipilimumab and a peptide vaccine had a median survival of 10 months compared with 6.4 months with the vaccine alone.
Ongoing follow-up of patients who received ipilimumab shows that complete responses can continue for >6 years in some patients. However, only 10.9% of the patients receiving ipilimumab (N = 676) showed complete or partial response, as with other targeted therapies, which work on subsets of patients.
A new study (study 024) has now shown that ipilimumab is also effective in previously untreated pa tients with metastatic melanoma. In this study, ipilimumab chemotherapy (dacarbazine) im proved OS compared with chemo therapy alone.
Ipilimumab is associated with severe adverse events, which may require immunosuppressive therapy with steroids. Because of the potential for life-threatening complications, patients receiving this drug may require a multidisciplinary team to manage them.
The common adverse effects associated with ipilimumab include fatiguediarrhea, skin rash, endocrine deficiencies (gland or hormone), and inflammation of the intestines (colitis). Severe-to-fatal autoimmune reactions were seen in 12.9% of patients treated with ipilimumab. (March 25, 2011)
