A randomized clinical trial of patients with advanced metastatic melanoma treated with ipilimumab (Yervoy), an immune checkpoint inhibitor, in combination with sargramostim (Leukine), an immune stimulant, vs ipilimumab alone, has found a 1-year survival rate of 68.9% vs 52.9% in the ipilimumab-only group. In addition, patients treated with the combination therapy experienced fewer serious adverse side effects than those treated with ipilimumab alone. The study by F. Stephen Hodi, MD, Director of the Melanoma Treatment Center and Director of the Center for Immuno-Oncology at Dana-Farber Cancer Institute, and colleagues is published in JAMA.1
Study Methodology
The Eastern Cooperative Oncology Group (ECOG) conducted a phase II randomized clinical from December 2010 to July 2011, enrolling 245 patients with stage III/IV metastatic melanoma who had received at least one prior therapy.
The patients were randomly assigned to receive ipilimumab plus sargramostim (granulocyte-macrophage colony-stimulating factor) vs ipilimumab alone. The primary end point was a comparison of length of overall survival. The secondary endpoint was progression-free survival, response rate, safety, and tolerability. The patients were followed for a median of 13.3 months.
Key Findings
The researchers found that the median overall survival for the ipilimumab-plus-sargramostim group was 17.5 months vs 12.7 months for the ipilimumab-only group. The 1-year survival rate for the combination therapy was 68.9% compared to 52.9% for ipilimumab alone (P = .01). In both groups, however, the median progression-free survival was similar, at 3.1 months. In addition, grade 3 to 5 adverse events occurred in 44.9% of patients in the ipilimumab-plus-sargramostim group vs 58.3% of patients in the ipilimumab-alone group.
“Among patients with unresectable stage III or IV melanoma, treatment with ipilimumab plus sargramostim vs ipilimumab alone resulted in longer [overall survival] and lower toxicity, but no difference in [progression-free survival]. These findings require confirmation in larger studies with longer follow-up,” concluded the researchers.
“This [study] opens the possibility of improving clinical outcomes and decreasing serious side effects in treating advanced melanoma with ipilimumab,” said Dr. Hodi in a statement. ■
Disclosure: The research was supported by Public Health Service Grants, the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. For full disclosures of the study authors, visit jama.jamanetwork.com.
Reference
1. Hodi FS, Lee S, McDermott DF, et al: Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: A randomized clinical trial. JAMA 312:1744-1753, 2014.
