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

2005; Lippincott Williams & Wilkins; Volume: 23; Issue: 16_suppl Linguagem: Inglês

10.1200/jco.2005.23.16_suppl.2575

1527-7755

Jennifer M. Gurney, Matthew T. Hueman, Michael Woll, Gayle B. Ryan, Catherine E. Storrer, Christine M. Fisher, Craig D. Shriver, Constantin G. Ioannides, Sathibalan Ponniah, George E. Peoples,

Monoclonal and Polyclonal Antibodies Research

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.