Randomized, Placebo-Controlled, Phase III Trial of Yeast-Derived Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients With No Evidence of Disease After Complete Surgical Resection of Locally Advanced and/or Stage IV Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E4697)

• Type of Material: Article
• Authors: David H Lawson, Emory University; Ahmad Tarhini, Emory University; Sandra Lee, Dana Farber Cancer Institute; Fengmin Zhao, Dana Farber Cancer Institute; Kim A. Margolin, Seattle Cancer Care Alliance; Marc S. Ernstoff, Dartmouth Hitchcock Medical Center; Michael B. Atkins, Beth Israel Deaconess Medical Center; Gary I. Cohen, Greater Baltimore Medical Center; Theresa L. Whiteside, University of Pittsburgh; Lisa H. Butterfield, University of Pittsburgh
• Language: English
• Date: 2015-12-01
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2015.62.0500
• Title of Journal or Parent Work: Journal of Clinical Oncology
• Volume: 33
• Issue: 34
• Start Page: 4066
• End Page: 4076
• Grant/Funding Information: Supported in part by Public Health Service Grants No. CA180802, CA180794, CA180864, CA180844, CA180854, CA18082, CA32102, CA180888, CA20319, CA31946, and CA04326 (for coordination by the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group, Robert L. Comis, MD, and Mitchell D. Schnall, MD, PhD, group co-chairs); by National Institutes of Health Grant No. P30CA047904 (through use of the Eastern Cooperative Oncology Group Central Immunology Laboratory [Frontier Science and Technology Research Foundation] at the University of Pittsburgh Cancer Institute Immunological Monitoring and Cellular Products Laboratory for this and correlative studies); and by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. Go to:
• Keywords: Oncology; ADJUVANT THERAPY; Science & Technology; HIGH-DOSE INTERFERON-ALPHA-2B; SARGRAMOSTIM; INTERGROUP; METASTATIC MELANOMA; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology

Abstract

Purpose We conducted a double-blind, placebo-controlled trial to evaluate the effect of granulocytemacrophage colony-stimulating factor (GM-CSF) and peptide vaccination (PV) on relapse-free survival (RFS) and overall survival (OS) in patients with resected high-risk melanoma. 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-A2â€"positive patients were randomly assigned to receive GM-CSF, PV, both, or placebo; HLA-A2â€"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-CSFâ€"treated patients with resected visceral metastases. When survival in HLA-A2â€"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.