Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients:: US military cancer institute clinical trials group study I-01 and I-02

被引：146

作者：

Peoples, George E. ^{[1
,2
]}

Holmes, Jarrod P. ^{[2
,3
]}

Hueman, Matthew T. ^{[2
,4
]}

Mittendorf, Elizabeth A. ^{[5
]}

Amin, Asna ^{[2
,4
]}

Khoo, Steven ^{[2
,4
]}

Dehqanzada, Zia A. ^{[2
,4
]}

Gurney, Jennifer M. ^{[2
]}

Woll, Michael M. ^{[2
]}

Ryan, Gayle B. ^{[2
]}

Storrer, Catherine E. ^{[2
]}

Craig, Dianna ^{[6
]}

Loannides, Constantin G. ^{[5
]}

Ponniah, Sathibalan ^{[2
]}

机构：

[1] Brooke Army Med Ctr, Dept Surg, Gen Surg Serv, Ft Sam Houston, TX 78234 USA

[2] Uniformed Serv Univ Hlth Sci, US Mil Canc Inst, Canc Vaccine Dev Program, Bethesda, MD 20814 USA

[3] Natl Naval Med Ctr, Dept Med, Div Hematol & Med Oncol, Bethesda, MD USA

[4] Walter Reed Army Med Ctr, Dept Surg, Gen Surg Serv, Washington, DC 20307 USA

[5] UT MD Anderson Canc Ctr, Houston, TX USA

[6] Windber Med Ctr, Joyce Murtha Breast Care Ctr, Windber, PA USA

来源：

CLINICAL CANCER RESEARCH | 2008年 / 14卷 / 03期

关键词：

D O I：

10.1158/1078-0432.CCR-07-1448

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：797 / 803

页数：7

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