The US Food and Drug Administration (FDA) on March 25 approved ipilimumab (Yervoy, Bristol-Myers Squibb) as immunotherapy for patients with late-stage melanoma, based on studies showing it improved survival outcomes in these difficult-to-treat patients.
Advanced melanoma is the leading cause of death from skin cancer, and there are few effective therapeutic options. Ipilimumab is the first drug approved for metastatic melanoma in 13 years and is the first drug ever to demonstrate overall survival improvement for this disease.
Ipilimumab works by blocking CTLA-4 (cytotoxic T-lymphocyte–associated antigen 4), thereby enhancing antitumor T-cell responses. Its approval is based on phase III trial results showing that the drug achieved its primary endpoint of extending overall survival among previously untreated patients with advanced melanoma. Overall survival was greater among patients randomized to chemotherapy plus ipilimumab, compared with those treated just with chemotherapy. Details of the trial will be presented at an upcoming medical meeting.
Results of an earlier study of ipilimumab that included 676 patients with unresectable stage III or IV metastatic melanoma were published in the June 2010 issue of the New England Journal of Medicine. Lead investigator F. Stephen Hodi, MD, of Dana Farber Cancer Institute, and colleagues reported that patients who received ipilimumab either alone or with a gp100 (glycoprotein 100) peptide vaccine had a median survival of about 10 months, compared with 6.4 months for patients receiving gp100 alone (P < .0003), which translated to a 34% reduction in the risk of death for the patients treated with ipilimumab. There were 14 deaths (2.1%) related to the study drugs, 7 of which were associated with immune-related adverse events, the investigators said.
Owing to safety concerns, ipilimumab is being approved along with a plan to inform healthcare professionals and patients about important side effects that can occur with this treatment.
“This is a landmark advance for several reasons,” Thomas Gajewski, MD, PhD, of the University of Chicago, who is President of the Society for Immunotherapy of Cancer. “First, this is a completely new way to treat cancer, by blocking a negative regulator of the immune response. Second, it is the first drug ever to show improved survival of metastatic melanoma patients. And third, we learned that clinical responses to immune therapies such as this one can take time, requiring some patience. FDA approval of this drug further strengthens the case for cancer immunotherapy. We anticipate other novel immune therapies that will benefit patients with cancer over the coming years.”