CHICAGO — After a 30-year drought during which 70 randomized trials failed to improve outcomes in advanced melanoma, the first agent in a new class of drugs has prolonged survival of advanced, pretreated patients in a large international phase III trial.
“This is the first time we have shown a survival benefit in metastatic melanoma,” Dr. Steven O’Day, the lead investigator, announced at the annual meeting of the American Society of Clinical Oncology.
The new agent, ipilimumab, is a monoclonal antibody targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), a gene that limits the ability of T cells to attack cancerous cells.
Median overall survival reached 10.1 months in 137 patients whose only active treatment was ipilimumab and 10 months in 403 patients given ipilimumab with an experimental vaccine. It was 6.4 months in 136 patients who received the vaccine without ipilimumab – a length of time that falls within the 6-9 month life expectancy for patients with metastatic melanoma, according to Dr. O’Day, chief of research and director of the melanoma program at the Angeles Clinic and Research Institute in Los Angeles.
The difference between the study arms treated with ipilimumab and patients who received only the vaccine was highly significant with a hazard ratio of 0.68 (P= .0004).
The one-year survival rate was nearly twice as high in the ipilimumab arms (46% vs. 25%), as was the two-year rate (24% vs. 14%). Some long-term survivors continue to be followed 4.5 years after treatment.
Disease-control rates were also significantly higher in the two ipilimumab arms (28.5% with ipilimumab alone and 20.1% with ipilimumab plus vaccine vs. 11% with the vaccine alone). Best overall response rates likewise were higher (10.9% and 5.7%, respectively, vs. 1.5%).
Addition of the GP 100 peptide vaccine did not appear to improve outcomes, Dr. O’Day noted. The investigators chose it for the control arm because it had drawn responses in a previous trial, and there is no standard of care for these patients. Dacarbazine (DTIC) has long and often been used, but no randomized trial has ever proven it superior to best supportive care.
Disclosures included that research funding was provided by Medarex and Bristol-Myers Squibb, which is developing ipilimumab.