Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02.

Abstract

PURPOSE:

E75 is an immunogenic peptide from the HER2/neu protein, which is overexpressed in many breast cancer patients. We have conducted two overlapping E75 vaccine trials to prevent recurrence in node-positive (NP) and node-negative (NN) breast cancer patients.

EXPERIMENTAL DESIGN:

E75 (HER2/neu 369-377) + granulocyte macrophage colony-stimulating factor was given intradermally to previously treated, disease-free NP breast cancer patients in a dose escalation safety trial and to NN breast cancer patients in a dose optimization study. Local and systemic toxicity was monitored. Immunologic responses were assessed using in vitro assays and in vivo delayed-type hypersensitivity responses. Clinical recurrences were documented.

RESULTS:

One hundred and eighty-six patients were enrolled in the two studies (NP, 95; NN, 91). Human leucocyte antigen A2 (HLA-A2) and HLA-A3 patients were vaccinated (n = 101), whereas all others (n = 85) were followed prospectively as controls. Toxicities were minimal, and a dose-dependent immunologic response to the vaccine was shown. Planned primary analysis revealed a recurrence rate of 5.6% in vaccinated patients compared with 14.2% in the controls (P = 0.04) at a median of 20 months follow-up. As vaccine-specific immunity waned over time, the difference in recurrence lost significance at 26 months median follow-up (8.3% versus 14.8%); however, a significant difference in the pattern of recurrence persisted.

CONCLUSIONS:

E75 is safe and effective in raising a dose-dependent HER2/neu immunity in HLA-A2 and HLA-A3 NP and NN breast cancer patients. More importantly, E75 may reduce recurrences in disease-free, conventionally treated, high-risk breast cancer patients. These findings warrant a prospective, randomized phase III trial of the E75 vaccine with periodic booster to prevent breast cancer recurrences.

• Authors: George E Peoples, Jarrod P Holmes, Matthew T Hueman, Elizabeth A Mittendorf, Asna Amin, Steven Khoo, Zia A Dehqanzada, Jennifer M Gurney, Michael M Woll, Gayle B Ryan, Catherine E Storrer, Dianna Craig, Constantin G Ioannides, Sathibalan Ponniah
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 3 Pg. 797-803 (Feb 01 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18245541 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Annexin A5
• Cancer Vaccines
• DNA Primers
• HLA-A2 Antigen
• HLA-A3 Antigen
• Receptor, ErbB-2

Topics

• Annexin A5 (analysis)
• Breast Neoplasms (immunology, prevention & control)
• Cancer Vaccines (therapeutic use)
• Cell Division (immunology)
• Cell Line, Tumor
• DNA Primers
• Female
• HLA-A2 Antigen (blood)
• HLA-A3 Antigen (blood)
• Humans
• Military Medicine
• Receptor, ErbB-2 (genetics, immunology)
• Recurrence
• Safety
• United States