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

George E. Peoples, Jarrod P. Holmes, Matthew Timothy 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

Research output: Contribution to journalArticle

Abstract

Purpose: E75 is an immunogenic peptide fromthe 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 A 2 (HLA-A 2) and HLA-A 3 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.

Original languageEnglish (US)
Pages (from-to)797-803
Number of pages7
JournalClinical Cancer Research
Volume14
Issue number3
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

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Vaccines
Clinical Trials
Breast Neoplasms
Recurrence
Neoplasms
Immunity
HLA-A3 Antigen
HLA-A2 Antigen
HLA-A Antigens
Delayed Hypersensitivity
Granulocyte-Macrophage Colony-Stimulating Factor
HLA Antigens
varespladib methyl
Research Design
Safety
Peptides
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / Peoples, George E.; Holmes, Jarrod P.; Hueman, Matthew Timothy; Mittendorf, Elizabeth A.; Amin, Asna; Khoo, Steven; Dehqanzada, Zia A.; Gurney, Jennifer M.; Woll, Michael M.; Ryan, Gayle B.; Storrer, Catherine E.; Craig, Dianna; Ioannides, Constantin G.; Ponniah, Sathibalan.

In: Clinical Cancer Research, Vol. 14, No. 3, 01.02.2008, p. 797-803.

Research output: Contribution to journalArticle

Peoples, GE, Holmes, JP, Hueman, MT, Mittendorf, EA, Amin, A, Khoo, S, Dehqanzada, ZA, Gurney, JM, Woll, MM, Ryan, GB, Storrer, CE, Craig, D, Ioannides, CG & Ponniah, S 2008, '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', Clinical Cancer Research, vol. 14, no. 3, pp. 797-803. https://doi.org/10.1158/1078-0432.CCR-07-1448
Peoples, George E. ; Holmes, Jarrod P. ; Hueman, Matthew Timothy ; Mittendorf, Elizabeth A. ; Amin, Asna ; Khoo, Steven ; Dehqanzada, Zia A. ; Gurney, Jennifer M. ; Woll, Michael M. ; Ryan, Gayle B. ; Storrer, Catherine E. ; Craig, Dianna ; Ioannides, Constantin G. ; Ponniah, Sathibalan. / 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. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 3. pp. 797-803.
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abstract = "Purpose: E75 is an immunogenic peptide fromthe 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 A 2 (HLA-A 2) and HLA-A 3 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.",
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T1 - Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients

T2 - U.S. Military Cancer Institute Clinical Trials Group study I-01 and I-02

AU - Peoples, George E.

AU - Holmes, Jarrod P.

AU - Hueman, Matthew Timothy

AU - Mittendorf, Elizabeth A.

AU - Amin, Asna

AU - Khoo, Steven

AU - Dehqanzada, Zia A.

AU - Gurney, Jennifer M.

AU - Woll, Michael M.

AU - Ryan, Gayle B.

AU - Storrer, Catherine E.

AU - Craig, Dianna

AU - Ioannides, Constantin G.

AU - Ponniah, Sathibalan

PY - 2008/2/1

Y1 - 2008/2/1

N2 - Purpose: E75 is an immunogenic peptide fromthe 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 A 2 (HLA-A 2) and HLA-A 3 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.

AB - Purpose: E75 is an immunogenic peptide fromthe 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 A 2 (HLA-A 2) and HLA-A 3 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.

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