TY - JOUR
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 T.
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.
UR - http://www.scopus.com/inward/record.url?scp=38949139497&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-07-1448
DO - 10.1158/1078-0432.CCR-07-1448
M3 - Article
C2 - 18245541
AN - SCOPUS:38949139497
SN - 1078-0432
VL - 14
SP - 797
EP - 803
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 3
ER -