Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients

2575 Background: E75 is an immunogenic peptide from the HER2/neu protein that is highly expressed in breast cancer. We are conducting a clinical trial of an E75 (+GM-CSF) vaccine to assess for safety, immunologic response, and the prevention of clinical recurrences in node-positive breast cancer (NPBC) patients without evidence of disease. Methods: Fifty-three NPBC patients have been enrolled thus far and HLA typed. HLA-A2+ patients (n=24) have been vaccinated while HLA-A2- patients (n=29) are being followed prospectively as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence are being measured. Results: Only minor toxicities have occurred (one grade 3 (4%)). All patients have demonstrated clonal expansion of E75-specific CD8+ T cells that lysed HER2/neu-expressing tumor cells. An optimal dosage and schedule have been established. Patients have developed delayed-type hypersensitivity (DTH) reactions to E75 post-vaccination compared to control (33 vs 7 mm, p<0.01). HLA-A2+ patients have been found to have larger, more poorly differentiated, and more hormonally-insensitive tumors compared to the HLA-A2- patients. Despite this, the only two deaths have occurred in the control group. The disease-free survival in the vaccinated group is 85.7% compared to 59.8% in the controls at 22 months median follow-up with a recurrence rate of 8% compared to 21%, respectively (p<0.19). Median time to recurrence in the vaccinated patients was prolonged (11 vs 8 months), and recurrence correlated with a weak DTH response. Conclusions: This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity appears to reduce the recurrence rate in high-risk NPBC patients. No significant financial relationships to disclose.