Patients with inoperable metastatic melanoma now have another treatment option as ipilimumab becomes the second immunotherapy drug approved by the US Food and Drug Administration (FDA) for the treatment of cancer. Fortunately for clinicians, ipilimumab also has a new, easier-to-pronounce name–Yervoy. Specifically, Yervoy is indicated for patients with unresectable metastatic melanoma that is newly diagnosed or continues to progress despite prior therapy.
Ipilimumab is a recombinant, human monoclonal antibody. It inhibits cytotoxic T-lymphocyte antigen-4 (CTLA-4), a protein involved in down-regulating T-cells to keep the immune system from attacking healthy tissue. Ipilimumab blocks CTLA-4 so that the T-cells remain active and the patient's immune system continues to fight the cancer as long as he or she is receiving treatment.
Data from a pivotal phase III trial of ipilimumab, which were published in the New England Journal of Medicine in 2010, show that patients who received ipilimumab alone or in combination with gp100 had better survival outcomes than patients treated only with gp100. Median overall survival (OS) for patients in the ipilimumab trial arms reached 10 months compared with 6 months for patients in the gp100 monotherapy arm.
The rate of 1-year survival was 46% for patients treated with ipilimumab versus 25% for patients given only gp100. Investigators estimated the 2-year survival rate at 24% for the ipilimumab group and 14% for the gp100 arm. Ipilimumab was associated with a 34% reduction in risk of death (hazard ratio, 0.66; P = .0026).
The overall response rate (ORR) was only 10.9% for patients receiving ipilimumab, but this was significantly higher than the ORR seen in the combination arm and the gp100 monotherapy group (5.7% vs 1.5%, respectively). The authors reported that the mean duration of response was 11.5 months for the group that received ipilimumab and gp100 combined and had not been reached in the other groups because >50% of patients who experienced complete or partial responses had not relapsed.
Approximately 10% of patients discontinued ipilimumab because of treatment-related adverse events. Among patients receiving ipilimumab alone, the most common adverse events (all grades) were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%) and colitis (8%). Some patients treated with ipilimumab did have severe or fatal immune-mediated adverse reactions, including enterocolitis (7%), edocrinopathy (4%), dermatitis (2), hepatitis (1%), neuropathy (1%), nephritis (1%), and eosinophilia (1%). Some of these can be treated with corticosteroids, according to researchers from one of the institutions that conducted ipilimumab trials.
In a review article on the drug, published in Seminars in Oncology (2010;37(5):440-449), Boasberg and colleagues also warn that "colonic perforation can occur" and call for patients who develop diarrhea to be monitored carefully, "with strict adherence to treatment algorithms." They note that if adverse effects are caught promptly and managed properly, "ipilimumab is an extremely safe drug to administer."
Bristol-Myers Squibb, which manufactures the drug, has worked with the FDA to develop a Risk Evaluation and Mitigation Strategy (REMS) for ipilimumab to help clinicians manage or prevent the most serious adverse-events. The company also announced that it has a copayment program to assist "eligible, commercially insured patients who have been prescribed ipilimumab" per FDA approval, and information is available at www.yervoy.com. The immunotherapy agent is being investigated in several other malignancies, and researchers are optimistic about outcomes.