FROM JOURNAL OF CLINICAL ONCOLOGY

Neither adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) nor a peptide vaccination (PV) significantly improved relapse-free or overall survival in patients with high-risk stage III and IV melanoma who had already undergone surgical resection, according to a study published online Sept. 8 in the Journal of Clinical Oncology.

Findings from early clinical trials support the possible benefit of GM-CSF as adjuvant therapy for melanoma, said the authors, led by Dr. David H. Lawson of Winship Cancer Institute, Emory University, Atlanta. Some studies have also shown that combining cytokines, including GM-CSF, with melanoma vaccines yields augmented immunologic responses and clinically significant tumor responses.

However, the improvement in survival in the current study did not reach statistical significance. The median survival for patients who received GM-CSF was 69.6 months, compared to 59.3 months for the patients who received placebo. This represented a 17.4% improvement in patients who received GM-CSF, but it was less than the projected absolute increase of 13.3 months and the relative improvement of 33% required for significance (HR, 0.94; 95% repeated CI, 0.77 to 1.15; stratified log-rank P =.528).

The results for relapse-free survival also did not reach statistical significance. For patients treated with GM-CSF it was 11.4 months (95% CI,9.4 to 14.8 months) compared to 8.8 month in the placebo group (95% CI, 7.5 to 11.2 months), which was an increase of 2.6 months, or 30% (HR, 0.88; 95% CI,0.74 to 1.04; stratified log-rank P = .131).

Just over half of the cohort (53.3%) were HLA-A2–positive patients. This group was randomized to receive PV alone or with GM-CSF, or placebo. The median overall survival was 68.6 months (95% CI, 47.0 to 92.3 months) in patients who received PV and 63.3 months (95% CI,49.2 to 105.0 months) for those who received placebo (HR, 0.93; 95% CI0.71 to1.21; P = .598)

Also in this subgroup, the median relapse-free survival was only 1.7 months longer in patients who received PV than for those who got placebo (11.5 v 9.8 months, for a 17.3% improvement). This was also lower than what was expected (3 months; 33% improvement), and also did not reach statistical significance.

Even though this study did not support their hypotheses, “trials that test GM-CSF in patients with resected visceral melanoma metastases are worthy of consideration,” wrote the authors. “GM-CSF may find its greatest use in melanoma in combination with other agents” (J Clin Oncol. 2015 Sep 8. doi:10.1200/JCO.2015.62.0500).

The study was supported by grants from the Public Health Service, National Institutes of Health, and the National Cancer Institute. Several of the coauthors report financial relationships with industry.

tor@frontlinemedcom.com

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