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

Authors

  • Elizabeth A. Mittendorf MD,

    1. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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  • Guy T. Clifton MD,

    1. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Ft. Sam Houston, Texas
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    • The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army, the Department of the Navy, or the Department of Defense.

  • Jarrod P. Holmes MD,

    1. Department of Hematology and Medical Oncology, Naval Medical Center San Diego, San Diego, California
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  • Kevin S. Clive MD,

    1. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Ft. Sam Houston, Texas
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  • Ritesh Patil MD,

    1. Joyce Murtha Breast Cancer Center, Windber, Pennsylvania and Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
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  • Linda C. Benavides MD,

    1. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Ft. Sam Houston, Texas
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  • Jeremy D. Gates MD,

    1. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Ft. Sam Houston, Texas
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  • Alan K. Sears MD,

    1. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Ft. Sam Houston, Texas
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  • Alexander Stojadinovic MD,

    1. Department of Surgery, Walter Reed Army Medical Center, Washington, District of Columbia
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  • Sathibalan Ponniah PhD,

    1. Cancer Vaccine Development Program, United States Military Cancer Institute, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland
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  • George E. Peoples MD

    Corresponding author
    1. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Ft. Sam Houston, Texas
    2. Cancer Vaccine Development Program, United States Military Cancer Institute, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland
    • Department of Surgery, General Surgery Service, Brooke Army Medical Center, 3851 Roger Brooke Drive, Ft. Sam Houston, TX 78234

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    • Fax: (210) 916-6658


  • The first 2 authors contributed equally to this article.

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. Cancer 2011. © 2011 American Cancer Society.

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