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

Cancer. 2012 May 15;118(10):2594-602. doi: 10.1002/cncr.26574. Epub 2011 Oct 11.


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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / immunology
  • Breast Neoplasms / mortality
  • Breast Neoplasms / prevention & control*
  • Cancer Vaccines / immunology*
  • Disease-Free Survival
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • HLA-A2 Antigen / blood
  • HLA-A3 Antigen / blood
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / prevention & control*
  • Peptide Fragments / immunology*
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / immunology*
  • Risk
  • T-Lymphocytes, Cytotoxic / immunology


  • Cancer Vaccines
  • HLA-A2 Antigen
  • HLA-A3 Antigen
  • Peptide Fragments
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • ERBB2 protein, human
  • Receptor, ErbB-2