Sargramostim, Ipilimumab Combination Improves Metastatic Melanoma Outcomes

Addition of sargramostim to ipilimumab extends overall survival and decreases the rate of high-grade adverse events in patients with advanced melanoma

medwireNews: Overall survival is prolonged and the incidence of high-grade adverse events is reduced in patients with unresectable stage III or IV metastatic melanoma treated with the combination of ipilimumab and sargramostim compared with ipilimumab treatment alone, research suggests.

However, progression-free survival was unaffected by the addition of sargramostim, a recombinant granulocyte macrophage colony-stimulating factor (GM-CSF), to the cytotoxic T-lymphocyte-associated Antigen (CTLA-4) inhibitor ipilimumab in this phase II trial.

“These results are consistent with the preclinical animal models and preliminary clinical experience of combining CTLA-4 blockade with GM-CSF-secreting whole-cell vaccines,” write the authors in JAMA.

Median overall survival was 17.5 months in the 123 patients who were randomly assigned to receive ipilimumab plus sargramostim compared with 12.7 months in the 122 participants treated with ipilimumab alone, a significant difference with a hazard ratio of 0.64.

The 1-year overall survival was 68.9% and 52.9% in the ipilimumab plus sargramostim and the ipilimumab alone groups, respectively, a difference that was also statistically significant.

However, F Stephen Hodi from Dana-Farber Cancer in Boston, Massachusetts, USA, and colleagues report that the median progression-free survival was 3.1 months in both the treatment groups.

They say: “The lack of correlation between overall survival and progression-free survival in this study presents challenges to clinical management and drug development because conventional radiographic criteria have not proven reliable for determining patient benefit.”

The researchers explain that both sargramostim and ipilimumab can induce inflammatory responses that could be confused for tumour progression and add that this “emphasizes the importance of end point selection when evaluating efficacy as well as the continued need for reliable predictive biomarkers.”

Patients treated with ipilimumab plus sargramostim had a significantly lower occurrence of grade 3 to 5 adverse events than those who received ipilimumab alone (44.9 vs 58.3%), with significant differences noted primarily in the pulmonary and gastrointestinal categories.

No participants who received ipilimumab plus sargramostim reported pulmonary problems compared with 7.5% of those given ipilimumab alone. The incidence of gastrointestinal adverse events was 16.1% in the patients given ipilimumab plus sargramostim versus 26.7% in those given ipilimumab alone.

F Stephen Hodi and co-workers conclude: “These findings require confirmation in larger sample sizes and with longer follow-up.”


Hodi FS, Lee S, McDermott DF, et al. Ipilimumab Plus Sargramostim vs Ipilimumab Alone for Treatment of Metastatic Melanoma: A Randomized Clinical Trial. JAMA 2014;312: 1744-1753. doi:10.1001/jama.2014.13943

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