Abstract | PURPOSE: PATIENTS AND METHODS: Patients with completely resected stage IV or high-risk stage III melanoma were grouped by human leukocyte antigen (HLA) -A2 status. HLA-A2-positive patients were randomly assigned to receive GM-CSF, PV, both, or placebo; HLA-A2-negative patients, GM-CSF or placebo. Treatment lasted for 1 year or until recurrence. Efficacy analyses were conducted in the intent-to-treat population. RESULTS: A total of 815 patients were enrolled. There were no significant improvements in OS (stratified log-rank P = .528; hazard ratio, 0.94; 95% repeated CI, 0.77 to 1.15) or RFS (P = .131; hazard ratio, 0.88; 95% CI, 0.74 to 1.04) in the patients assigned to GM-CSF (n = 408) versus those assigned to placebo (n = 407). The median OS times with GM-CSF versus placebo treatments were 69.6 months (95% CI, 53.4 to 83.5 months) versus 59.3 months (95% CI, 44.4 to 77.3 months); the 5-year OS probability rates were 52.3% (95% CI, 47.3% to 57.1%) versus 49.4% (95% CI, 44.3% to 54.3%), respectively. The median RFS times with GM-CSF versus placebo were 11.4 months (95% CI, 9.4 to 14.8 months) versus 8.8 months (95% CI, 7.5 to 11.2 months); the 5-year RFS probability rates were 31.2% (95% CI, 26.7% to 35.9%) versus 27.0% (95% CI, 22.7% to 31.5%), respectively. Exploratory analyses showed a trend toward improved OS in GM-CSF-treated patients with resected visceral metastases. When survival in HLA-A2-positive patients who received PV versus placebo was compared, RFS and OS were not significantly different. Treatment-related grade 3 or greater adverse events were similar between GM-CSF and placebo groups. CONCLUSION: Neither adjuvant GM-CSF nor PV significantly improved RFS or OS in patients with high-risk resected melanoma. Exploratory analyses suggest that GM-CSF may be beneficial in patients with resected visceral metastases; this observation requires prospective validation.
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Authors | David H Lawson, Sandra Lee, Fengmin Zhao, Ahmad A Tarhini, Kim A Margolin, Marc S Ernstoff, Michael B Atkins, Gary I Cohen, Theresa L Whiteside, Lisa H Butterfield, John M Kirkwood |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 33
Issue 34
Pg. 4066-76
(Dec 01 2015)
ISSN: 1527-7755 [Electronic] United States |
PMID | 26351350
(Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Copyright | © 2015 by American Society of Clinical Oncology. |
Chemical References |
- HLA-A2 Antigen
- Peptide Fragments
- Vaccines, Subunit
- Granulocyte-Macrophage Colony-Stimulating Factor
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Cohort Studies
- Double-Blind Method
- Female
- Follow-Up Studies
- Granulocyte-Macrophage Colony-Stimulating Factor
(administration & dosage)
- HLA-A2 Antigen
(immunology)
- Humans
- Male
- Melanoma
(mortality, pathology, therapy)
- Middle Aged
- Neoplasm Staging
- Peptide Fragments
(therapeutic use)
- Prognosis
- Skin Neoplasms
- Survival Rate
- Vaccination
- Vaccines, Subunit
(immunology)
- Young Adult
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