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Open Access 01-06-2020 | Breast Cancer | Clinical trial

Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence

Authors: Tommy A. Brown II, Elizabeth A. Mittendorf, Diane F. Hale, John W. Myers III, Kaitlin M. Peace, Doreen O. Jackson, Julia M. Greene, Timothy J. Vreeland, G. Travis Clifton, Alexandros Ardavanis, Jennifer K. Litton, Nathan M. Shumway, J. Symanowski, James L. Murray, Sathibalan Ponniah, E. A. Anastasopoulou, N. F. Pistamaltzian, Constantin N. Baxevanis, Sonia A. Perez, Michael Papamichail, George E. Peoples

Published in: Breast Cancer Research and Treatment | Issue 2/2020

Abstract

Purpose

AE37 and GP2 are HER2 derived peptide vaccines. AE37 primarily elicits a CD4+ response while GP2 elicits a CD8+ response against the HER2 antigen. These peptides were tested in a large randomized trial to assess their ability to prevent recurrence in HER2 expressing breast cancer patients. The primary analyses found no difference in 5-year overall disease-free survival (DFS) but possible benefit in subgroups. Here, we present the final landmark analysis.

Methods

In this 4-arm, prospective, randomized, single-blinded, multi-center phase II trial, disease-free node positive and high-risk node negative breast cancer patients enrolled after standard of care therapy. Six monthly inoculations of vaccine (VG) vs. control (CG) were given as the primary vaccine series with 4 boosters at 6-month intervals. Demographic, safety, immunologic, and DFS data were evaluated.

Results

456 patients were enrolled; 154 patients in the VG and 147 in CG for AE37, 89 patients in the VG and 91 in CG for GP2. The AE37 arm had no difference in DFS as compared to CG, but pre-specified exploratory subgroup analyses showed a trend towards benefit in advanced stage (p = 0.132, HR 0.573 CI 0.275–1.193), HER2 under-expression (p = 0.181, HR 0.756 CI 0.499–1.145), and triple-negative breast cancer (p = 0.266, HR 0.443 CI 0.114–1.717). In patients with both HER2 under-expression and advanced stage, there was significant benefit in the VG (p = 0.039, HR 0.375 CI 0.142–0.988) as compared to CG. The GP2 arm had no significant difference in DFS as compared to CG, but on subgroup analysis, HER2 positive patients had no recurrences with a trend toward improved DFS (p = 0.052) in VG as compared to CG.

Conclusions

This phase II trial reveals that AE37 and GP2 are safe and possibly associated with improved clinical outcomes of DFS in certain subgroups of breast cancer patients. With these findings, further evaluations are warranted of AE37 and GP2 vaccines given in combination and/or separately for specific subsets of breast cancer patients based on their disease biology.

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Title: Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence
Authors: Tommy A. Brown II
Elizabeth A. Mittendorf
Diane F. Hale
John W. Myers III
Kaitlin M. Peace
Doreen O. Jackson
Julia M. Greene
Timothy J. Vreeland
G. Travis Clifton
Alexandros Ardavanis
Jennifer K. Litton
Nathan M. Shumway
J. Symanowski
James L. Murray
Sathibalan Ponniah
E. A. Anastasopoulou
N. F. Pistamaltzian
Constantin N. Baxevanis
Sonia A. Perez
Michael Papamichail
George E. Peoples
Publication date: 01-06-2020
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 2/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05638-x

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