Abstract P2-20-03: Combination Immunotherapy for Breast Cancer Patients: Safety and Immunologic Data from a Phase II Trial Administering a HER2/neu-Derived Peptide vaccine (AE37+GM-CSF) Sequentially or Concurrently with Trastuzumab in the Adjuvant Setting
Authors: Mittendorf EA , Perez SA , Tzonis P , Clifton GT , Ardavanis A , Holmes JP , Lekka E , Baxevanis CN , Ponniah B , Peoples GE , Papamichail M. 
Published: April 2011

Abstract
Background. AE37 is a HER2-derived peptide (AA:776-790) modified to enhance antigen-specific stimulation of CD4+ T cells. A phase I trial has shown that AE37 mixed with GM-CSF (GM) is safe and effective in raising HER2-specific immunity. Our group is conducting a prospective, randomized, single-blinded phase II clinical trial of AE37+GM vs GM alone. The goal of the current study is to determine the effects on cardiac safety and immunologic response of vaccinating sequentially or concurrently with administration of trastuzumab (Tz). Methods. The trial is enrolling high-risk breast cancer patients with tumors having any degree of HER2 expression (IHC 1-3+). At the time of enrollment, all patients are disease-free having completed surgery, chemotherapy and when indicated, XRT. Patients receiving Tz as part of their standard therapy were administered the vaccine sequentially after completion of Tz or concurrently with Tz. Cardiac toxicity was assessed by determining ejection fraction (EF). Immunologic response was monitored by delayed-type hypersensitivity (DTH) responses and [3H]thymidine proliferative assays for the hybrid AE37 and native AE36 (unmodified AA:776-790) peptides.
Results. To date the trial has enrolled 102 patients at our international site, including 51 receiving Tz as part of standard therapy. Of these, 30 were randomized to receive AE37+GM; 13 sequentially after Tz (group 1) and 17 concurrently (group 2). 21 patients were randomized to receive GM alone. There was no change in EF pre-and post completion of vaccination series for patients in group 1 (mean 63±1.7% vs 65±2.9%, p=.32) or group 2 (mean 68±3.7% vs 63±%, p=.14). There was a statistically significant difference in DTH response pre-vs post-vaccination with AE37+GM in both group 1 (mean 1 mm vs 20 mm, p&lt;.001) and group 2 (2 mm vs 29 mm, p&lt;.001); however, there was no significant difference in the post-vaccination DTH response when comparing group 1 to group 2 (p=.16). There was no significant difference in the DTH response pre vs post inoculation for patients receiving GM alone. There was a significant proliferative response to AE36 and AE37 in both group 1 and 2 with the response greater in group 2. There was no proliferative response in patients receiving GM alone. Conclusions. Administration of the AE37+GM peptide vaccine with Tz administered either concurrently or sequentially is safe without any increase in the incidence of cardiotoxicity. Vaccination with AE37+GM concurrently with Tz results in enhanced proliferation suggesting that there may be clinical benefit to such a combination immunotherapy strategy. Patients will continue to be followed to determine the effects of vaccination with sequential vs concurrent Tz administration on clinical outcome. Figure available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-20-03.