PMID- 21989902
OWN - NLM
STAT- MEDLINE
DCOM- 20120621
LR  - 20211020
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 118
IP  - 10
DP  - 2012 May 15
TI  - Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer 
      recurrence in high-risk patients: from US Military Cancer Institute Clinical 
      Trials Group Study I-01 and I-02.
PG  - 2594-602
LID - 10.1002/cncr.26574 [doi]
AB  - BACKGROUND: The authors conducted exploratory phase 1-2 clinical trials 
      vaccinating breast cancer patients with E75, a human leukocyte antigen (HLA) 
      A2/A3-restricted HER-2/neu (HER2) peptide, and granulocyte-macrophage 
      colony-stimulating factor. The vaccine is given as adjuvant therapy to prevent 
      disease recurrence. They previously reported that the vaccine is safe and 
      effective in stimulating expansion of E75-specific cytotoxic T cells. Here, they 
      report 24-month landmark analyses of disease-free survival (DFS). METHODS: These 
      dose escalation/schedule optimization trials enrolled lymph node-positive and 
      high-risk lymph node-negative patients with HER2 (immunohistochemistry [IHC] 
      1-3(+) ) expressing tumors. HLA-A2/A3(+) patients were vaccinated; others were 
      followed prospectively as controls for recurrence. DFS was analyzed by 
      Kaplan-Meier curves; groups were compared using log-rank tests. RESULTS: Of 195 
      enrolled patients, 182 were evaluable: 106 (58.2%) in the vaccinated group and 76 
      (41.8%) in the control group. The 24-month landmark analysis DFS was 94.3% in the 
      vaccinated group and 86.8% in the control group (P = .08). Importantly, because 
      of trial design, 65% of patients received a lower than optimal vaccine dose. In 
      subset analyses, patients who benefited most from vaccination (vaccinated group 
      vs control group) had lymph node-positive (DFS, 90.2% vs 79.1%; P = .13), HER2 
      IHC 1+-2+ (DFS, 94.0% vs 79.4%; P = .04), or grade 1 or 2 (DFS, 98.4% vs 86.0%; P 
      = .01) tumors and were optimally dosed (DFS, 97.3% vs 86.8%; P = .08). A booster 
      program has been initiated; no patients receiving booster inoculations have 
      recurred. CONCLUSIONS: The E75 vaccine has clinical efficacy that is more 
      prominent in certain patients. A phase 3 trial enrolling lymph node-positive 
      patients with HER2 low-expressing tumors is warranted.
CI  - Copyright (c) 2011 American Cancer Society.
FAU - Mittendorf, Elizabeth A
AU  - Mittendorf EA
AD  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer 
      Center, Houston, TX, USA.
FAU - Clifton, Guy T
AU  - Clifton GT
FAU - Holmes, Jarrod P
AU  - Holmes JP
FAU - Clive, Kevin S
AU  - Clive KS
FAU - Patil, Ritesh
AU  - Patil R
FAU - Benavides, Linda C
AU  - Benavides LC
FAU - Gates, Jeremy D
AU  - Gates JD
FAU - Sears, Alan K
AU  - Sears AK
FAU - Stojadinovic, Alexander
AU  - Stojadinovic A
FAU - Ponniah, Sathibalan
AU  - Ponniah S
FAU - Peoples, George E
AU  - Peoples GE
LA  - eng
GR  - R00 CA133244/CA/NCI NIH HHS/United States
GR  - 4R00CA133244-03/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20111011
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Cancer Vaccines)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (HLA-A3 Antigen)
RN  - 0 (Peptide Fragments)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Breast Neoplasms/immunology/mortality/*prevention & control
MH  - Cancer Vaccines/*immunology
MH  - Disease-Free Survival
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/immunology
MH  - HLA-A2 Antigen/blood
MH  - HLA-A3 Antigen/blood
MH  - Humans
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*prevention & control
MH  - Peptide Fragments/*immunology
MH  - Receptor, ErbB-2/analysis/*immunology
MH  - Risk
MH  - T-Lymphocytes, Cytotoxic/immunology
PMC - PMC3428069
MID - NIHMS385833
COIS- CONFLICT OF INTEREST DISCLOSURES G.E.P. has partial inventor rights to E75 (owned 
      jointly by The University of Texas MD Anderson Cancer Center and the US 
      Government), and the patent was licensed to Apthera, Inc., Scottsdale, Arizona, 
      after completion of the described trials. Under the terms of the license, G.E.P. 
      is entitled to licensing revenues, and he also serves as a consultant to Apthera.
EDAT- 2011/10/13 06:00
MHDA- 2012/06/22 06:00
PMCR- 2013/05/15
CRDT- 2011/10/13 06:00
PHST- 2011/06/23 00:00 [received]
PHST- 2011/08/16 00:00 [revised]
PHST- 2011/08/24 00:00 [accepted]
PHST- 2011/10/13 06:00 [entrez]
PHST- 2011/10/13 06:00 [pubmed]
PHST- 2012/06/22 06:00 [medline]
PHST- 2013/05/15 00:00 [pmc-release]
AID - 10.1002/cncr.26574 [doi]
PST - ppublish
SO  - Cancer. 2012 May 15;118(10):2594-602. doi: 10.1002/cncr.26574. Epub 2011 Oct 11.