PMID- 26351350
OWN - NLM
STAT- MEDLINE
DCOM- 20160308
LR  - 20240325
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 33
IP  - 34
DP  - 2015 Dec 1
TI  - 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).
PG  - 4066-76
LID - 10.1200/JCO.2015.62.0500 [doi]
AB  - PURPOSE: We conducted a double-blind, placebo-controlled trial to evaluate the 
      effect of granulocyte-macrophage 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-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.
CI  - (c) 2015 by American Society of Clinical Oncology.
FAU - Lawson, David H
AU  - Lawson DH
AD  - David H. Lawson, Winship Cancer Institute of Emory University, Atlanta, GA; 
      Sandra Lee and Fengmin Zhao, Dana-Farber Cancer Institute; Michael B. Atkins, 
      Beth Israel Deaconess Medical Center, Boston, MA; Ahmad A. Tarhini, Theresa L. 
      Whiteside, Lisa H. Butterfield, and John M. Kirkwood, University of Pittsburgh 
      Medical Center, Pittsburgh, PA; Kim A. Margolin, Seattle Cancer Care Alliance, 
      Seattle, WA; Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 
      and Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD. 
      dlawson@emory.edu.
FAU - Lee, Sandra
AU  - Lee S
AD  - David H. Lawson, Winship Cancer Institute of Emory University, Atlanta, GA; 
      Sandra Lee and Fengmin Zhao, Dana-Farber Cancer Institute; Michael B. Atkins, 
      Beth Israel Deaconess Medical Center, Boston, MA; Ahmad A. Tarhini, Theresa L. 
      Whiteside, Lisa H. Butterfield, and John M. Kirkwood, University of Pittsburgh 
      Medical Center, Pittsburgh, PA; Kim A. Margolin, Seattle Cancer Care Alliance, 
      Seattle, WA; Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 
      and Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD.
FAU - Zhao, Fengmin
AU  - Zhao F
AD  - David H. Lawson, Winship Cancer Institute of Emory University, Atlanta, GA; 
      Sandra Lee and Fengmin Zhao, Dana-Farber Cancer Institute; Michael B. Atkins, 
      Beth Israel Deaconess Medical Center, Boston, MA; Ahmad A. Tarhini, Theresa L. 
      Whiteside, Lisa H. Butterfield, and John M. Kirkwood, University of Pittsburgh 
      Medical Center, Pittsburgh, PA; Kim A. Margolin, Seattle Cancer Care Alliance, 
      Seattle, WA; Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 
      and Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD.
FAU - Tarhini, Ahmad A
AU  - Tarhini AA
AD  - David H. Lawson, Winship Cancer Institute of Emory University, Atlanta, GA; 
      Sandra Lee and Fengmin Zhao, Dana-Farber Cancer Institute; Michael B. Atkins, 
      Beth Israel Deaconess Medical Center, Boston, MA; Ahmad A. Tarhini, Theresa L. 
      Whiteside, Lisa H. Butterfield, and John M. Kirkwood, University of Pittsburgh 
      Medical Center, Pittsburgh, PA; Kim A. Margolin, Seattle Cancer Care Alliance, 
      Seattle, WA; Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 
      and Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD.
FAU - Margolin, Kim A
AU  - Margolin KA
AD  - David H. Lawson, Winship Cancer Institute of Emory University, Atlanta, GA; 
      Sandra Lee and Fengmin Zhao, Dana-Farber Cancer Institute; Michael B. Atkins, 
      Beth Israel Deaconess Medical Center, Boston, MA; Ahmad A. Tarhini, Theresa L. 
      Whiteside, Lisa H. Butterfield, and John M. Kirkwood, University of Pittsburgh 
      Medical Center, Pittsburgh, PA; Kim A. Margolin, Seattle Cancer Care Alliance, 
      Seattle, WA; Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 
      and Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD.
FAU - Ernstoff, Marc S
AU  - Ernstoff MS
AD  - David H. Lawson, Winship Cancer Institute of Emory University, Atlanta, GA; 
      Sandra Lee and Fengmin Zhao, Dana-Farber Cancer Institute; Michael B. Atkins, 
      Beth Israel Deaconess Medical Center, Boston, MA; Ahmad A. Tarhini, Theresa L. 
      Whiteside, Lisa H. Butterfield, and John M. Kirkwood, University of Pittsburgh 
      Medical Center, Pittsburgh, PA; Kim A. Margolin, Seattle Cancer Care Alliance, 
      Seattle, WA; Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 
      and Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD.
FAU - Atkins, Michael B
AU  - Atkins MB
AD  - David H. Lawson, Winship Cancer Institute of Emory University, Atlanta, GA; 
      Sandra Lee and Fengmin Zhao, Dana-Farber Cancer Institute; Michael B. Atkins, 
      Beth Israel Deaconess Medical Center, Boston, MA; Ahmad A. Tarhini, Theresa L. 
      Whiteside, Lisa H. Butterfield, and John M. Kirkwood, University of Pittsburgh 
      Medical Center, Pittsburgh, PA; Kim A. Margolin, Seattle Cancer Care Alliance, 
      Seattle, WA; Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 
      and Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD.
FAU - Cohen, Gary I
AU  - Cohen GI
AD  - David H. Lawson, Winship Cancer Institute of Emory University, Atlanta, GA; 
      Sandra Lee and Fengmin Zhao, Dana-Farber Cancer Institute; Michael B. Atkins, 
      Beth Israel Deaconess Medical Center, Boston, MA; Ahmad A. Tarhini, Theresa L. 
      Whiteside, Lisa H. Butterfield, and John M. Kirkwood, University of Pittsburgh 
      Medical Center, Pittsburgh, PA; Kim A. Margolin, Seattle Cancer Care Alliance, 
      Seattle, WA; Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 
      and Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD.
FAU - Whiteside, Theresa L
AU  - Whiteside TL
AD  - David H. Lawson, Winship Cancer Institute of Emory University, Atlanta, GA; 
      Sandra Lee and Fengmin Zhao, Dana-Farber Cancer Institute; Michael B. Atkins, 
      Beth Israel Deaconess Medical Center, Boston, MA; Ahmad A. Tarhini, Theresa L. 
      Whiteside, Lisa H. Butterfield, and John M. Kirkwood, University of Pittsburgh 
      Medical Center, Pittsburgh, PA; Kim A. Margolin, Seattle Cancer Care Alliance, 
      Seattle, WA; Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 
      and Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD.
FAU - Butterfield, Lisa H
AU  - Butterfield LH
AD  - David H. Lawson, Winship Cancer Institute of Emory University, Atlanta, GA; 
      Sandra Lee and Fengmin Zhao, Dana-Farber Cancer Institute; Michael B. Atkins, 
      Beth Israel Deaconess Medical Center, Boston, MA; Ahmad A. Tarhini, Theresa L. 
      Whiteside, Lisa H. Butterfield, and John M. Kirkwood, University of Pittsburgh 
      Medical Center, Pittsburgh, PA; Kim A. Margolin, Seattle Cancer Care Alliance, 
      Seattle, WA; Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 
      and Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD.
FAU - Kirkwood, John M
AU  - Kirkwood JM
AD  - David H. Lawson, Winship Cancer Institute of Emory University, Atlanta, GA; 
      Sandra Lee and Fengmin Zhao, Dana-Farber Cancer Institute; Michael B. Atkins, 
      Beth Israel Deaconess Medical Center, Boston, MA; Ahmad A. Tarhini, Theresa L. 
      Whiteside, Lisa H. Butterfield, and John M. Kirkwood, University of Pittsburgh 
      Medical Center, Pittsburgh, PA; Kim A. Margolin, Seattle Cancer Care Alliance, 
      Seattle, WA; Marc S. Ernstoff, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 
      and Gary I. Cohen, Greater Baltimore Medical Center, Baltimore, MD.
LA  - eng
SI  - ClinicalTrials.gov/NCT01989572
GR  - CA20319/CA/NCI NIH HHS/United States
GR  - U10 CA180802/CA/NCI NIH HHS/United States
GR  - P50 CA121973/CA/NCI NIH HHS/United States
GR  - U10 CA066636/CA/NCI NIH HHS/United States
GR  - U10 CA032102/CA/NCI NIH HHS/United States
GR  - CA04326/CA/NCI NIH HHS/United States
GR  - U10 CA020319/CA/NCI NIH HHS/United States
GR  - CA180794/CA/NCI NIH HHS/United States
GR  - CA180844/CA/NCI NIH HHS/United States
GR  - U10 CA180864/CA/NCI NIH HHS/United States
GR  - R01 CA168628/CA/NCI NIH HHS/United States
GR  - N01 CA032102/CA/NCI NIH HHS/United States
GR  - U10 CA021115/CA/NCI NIH HHS/United States
GR  - P30 CA047904/CA/NCI NIH HHS/United States
GR  - U10 CA031946/CA/NCI NIH HHS/United States
GR  - CA180802/CA/NCI NIH HHS/United States
GR  - U24 CA196172/CA/NCI NIH HHS/United States
GR  - U10 CA180854/CA/NCI NIH HHS/United States
GR  - P30CA047904/CA/NCI NIH HHS/United States
GR  - CA18082/CA/NCI NIH HHS/United States
GR  - CA180854/CA/NCI NIH HHS/United States
GR  - U10 CA180820/CA/NCI NIH HHS/United States
GR  - U10 CA023318/CA/NCI NIH HHS/United States
GR  - CA180888/CA/NCI NIH HHS/United States
GR  - U10 CA180794/CA/NCI NIH HHS/United States
GR  - CA180864/CA/NCI NIH HHS/United States
GR  - U10 CA180888/CA/NCI NIH HHS/United States
GR  - UG1 CA233184/CA/NCI NIH HHS/United States
GR  - CA31946/CA/NCI NIH HHS/United States
GR  - U10 CA180844/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20150908
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Peptide Fragments)
RN  - 0 (Vaccines, Subunit)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cohort Studies
MH  - Double-Blind Method
MH  - Female
MH  - Follow-Up Studies
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*administration & dosage
MH  - HLA-A2 Antigen/*immunology
MH  - Humans
MH  - Male
MH  - Melanoma/*mortality/pathology/*therapy
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Peptide Fragments/*therapeutic use
MH  - Prognosis
MH  - Skin Neoplasms
MH  - Survival Rate
MH  - Vaccination
MH  - Vaccines, Subunit/*immunology
MH  - Young Adult
MH  - Melanoma, Cutaneous Malignant
PMC - PMC4669592
COIS- Authors' disclosures of potential conflicts of interest are found in the article 
      online at www.jco.org. Author contributions are found at the end of this article.
EDAT- 2015/09/10 06:00
MHDA- 2016/03/10 06:00
PMCR- 2016/12/01
CRDT- 2015/09/10 06:00
PHST- 2015/09/10 06:00 [entrez]
PHST- 2015/09/10 06:00 [pubmed]
PHST- 2016/03/10 06:00 [medline]
PHST- 2016/12/01 00:00 [pmc-release]
AID - JCO.2015.62.0500 [pii]
AID - 20500 [pii]
AID - 10.1200/JCO.2015.62.0500 [doi]
PST - ppublish
SO  - J Clin Oncol. 2015 Dec 1;33(34):4066-76. doi: 10.1200/JCO.2015.62.0500. Epub 2015 
      Sep 8.