title: 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.
abstract: 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.
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Elizabeth A
authors: EA
authors: Mittendorf
authors: Guy T
authors: GT
authors: Clifton
authors: Jarrod P
authors: JP
authors: Holmes
authors: Kevin S
authors: KS
authors: Clive
authors: Ritesh
authors: R
authors: Patil
authors: Linda C
authors: LC
authors: Benavides
authors: Jeremy D
authors: JD
authors: Gates
authors: Alan K
authors: AK
authors: Sears
authors: Alexander
authors: A
authors: Stojadinovic
authors: Sathibalan
authors: S
authors: Ponniah
authors: George E
authors: GE
authors: Peoples
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D019496:Cancer Vaccines / Q000276:immunology*; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D015789:HLA-A2 Antigen / Q000097:blood; D015791:HLA-A3 Antigen / Q000097:blood; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D010446:Peptide Fragments / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000276:immunology*; D012306:Risk; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human