Cancer vaccines may have the most potential for clinical impact when used in the adjuvant setting when tumor burden is at its lowest. Application of cancer vaccines in the adjuvant setting, however, requires integration of immunization with more standard cytotoxic or cytostatic therapies. Common adjuvant therapies for breast cancer patients, i.e. trastuzumab, bisphosphonates and hormonal agents are often administered over several years requiring concurrent administration of these drugs with active immunization. We questioned whether these common adjuvant therapies would impact a patient's ability to develop tumor specific immunity with vaccination. Immune parameters from 36 subjects were evaluated. We determined these adjuvant therapies have no impact on the ability to develop an immune response specific for HER-2/neu peptides (P>0.1) nor do they have an impact on the magnitude of T cell immunity developed with concurrent vaccination (P>0.1). This is the first report to show that the use of trastuzumab, bisphosphonates and hormonal therapy concurrent with cancer vaccine administration have no impact on either the generation or the magnitude of vaccine induced immunity.

2528 Background: HER2 is a tumor antigen in breast and ovarian cancer. Vaccines targeting both Class I and II epitopes of HER2 can elicit long-lived cellular immunity. Trastuzumab increases the activity of HER2-specific T cells in vitro. This study examines the safety and immunogenicity of a HER2 peptide vaccine given with trastuzumab to augment HER2-specific immune responses in vivo. Methods: 20 HLA-A2+ subjects will be enrolled on this Phase I/II single institution trial. Eligible subjects must have stage IV HER2 overexpressing breast or ovarian cancer, stable or no evident disease on maintenance trastuzumab and a normal baseline MUGA. Subjects must have ECOG performance status 0–1, creat ≤ 2.0, bili < 1.5 × ULN, SGOT < 2 × ULN. The HER2 vaccine used in this study has been previously reported and is composed of 3 HER2 Class II epitopes encompassing Class I epitopes in their natural sequence. (Knutson et al, J Clin Investigation 107:477–484, 2001). Subjects receive 6 vaccinations + GM-CSF at monthly intervals. Primary endpoints are safety and immunogenicity. Results: To date, 14 of 20 subjects have been enrolled. A total of 77 vaccinations have been given. Of 276 reported toxicities, 88% were Grade 1; most common were constitutional symptoms (25%), injection site reactions (14%), and cytopenias (14%). 11% of toxicities were Grade 2; most common were lymphopenia (34%) and headache (19%). There was one Grade 3 toxicity (syncope 5 hours after vaccination) and one Grade 4 toxicity (stroke secondary to brain metastases in long-term follow up). Cardiac toxicity included two Grade 2 asymptomatic decreases in LVEF (54 to 49% and 64 to 45%.) The average decrease in LVEF between baseline and 9 month post-vaccine follow up was 5% ± 5.85 (n = 10). Of the 10 patients who have had immunologic analysis performed at multiple time points, 5 have developed significant T cell immunity to either HER2 overlapping peptide pools and/or HER2 peptides. Complete immunologic analysis will be presented. Conclusions: Subjects with HER2 overexpressing Stage IV cancer can be safely immunized with a HER2 peptide vaccine while receiving concurrent trastuzumab without additional cardiac toxicity. In addition, the approach is immunogenic, generating significant levels of HER2-specific T cells in the peripheral blood. No significant financial relationships to disclose.

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