Among patients with metastatic melanoma, treatment with a combination of the drugs sargramostim plus ipilimumab, compared with ipilimumab alone, resulted in longer overall survival and lower toxicity, but no difference in progression-free survival. These findings were published in JAMA (2014;312[17]:1744-1753).

Ipilimumab is a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), which is an immune checkpoint molecule that inhibits T-lymphocyte activity. Sargramostim is a systemic granulocyte-macrophage colony stimulating factor (GM-CSF). The study explained that GM-CSF enhances the activation of dendritic cells for antigen presentation and potentiates T- and B-lymphocyte antitumor functions. The goal of the study was to determine if systemic administration of GM-CSF enhances the CTLA-4 blockade.

F. Stephen Hodi, MD, of the Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues conducted a phase 2 clinical trial involving 245 patients with unresectable (unable to be removed by surgery) stage Ill or IV melanoma. The patients were randomly assigned to receive ipilimumab (intravenously) on day 1 plus sargramostim (injected beneath the skin) on days 1 to 14 of a 21-day cycle (n = 123) or ipilimumab alone (n = 122). The researchers compared the effect of these treatments on length of overall survival, progression-free survival, response rate, safety, and tolerability.

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 Median follow-up was 13.3 months. The overall survival was significantly improved with the addition of sargramostim to ipilimumab. The median overall survival was 17.5 months for the ipilimumab plus sargramostim group and 12.7 months for the ipilimumab-only group.

The 1-year overall survival was 68.9% for the combination treatment group and 52.9% for the ipilimumab-only group. There was no difference in progression-free survival.

Adverse events were more common in the ipilimumab-only group. Toxicity was significantly lower in the ipilimumab plus sargramostim group than in the ipilimumab­only group.

“This randomized phase 2 study supports the evidence that the addition of sargramostim to ipilimumab therapy improved overall survival in patients with metastatic melanoma,” the authors wrote. “These findings require confirmation in larger sample sizes and with longer follow-up.”