Abstract P2-20-01: Safety and Clinical Efficacy of Multiple Booster Inoculations with the E75 Adjuvant Breast Cancer Vaccine

Abstract Background: We are conducting clinical trials of the HER2/neu E75-peptide+GM-CSF vaccine in clinically disease-free breast cancer patients at high risk for recurrence. Our Phase I/II trials have shown that the vaccine is safe and effective in stimulating clonal expansion of E75-specific CD8+ T-cells; however, this peptide-specific immunity decreases over time. Due to this waning immunity, a voluntary booster program was initiated. Methods: Node-positive and high-risk node-negative patients who were clinically disease-free after surgery and standard adjuvant therapy were enrolled. HLA-A2/A3+ patients were vaccinated (VG), while HLA-A2/A3-patients were followed as controls (CG). Patients who were ≥6 months from the completion of their primary vaccination series (PVS) were offered booster inoculations every 6 months. Patients were monitored for local and systemic toxicity. Orthagonal mean of local reactions (LR) were measured after each booster inoculation. In HLA-A2+ patients, E75-specific CD8+ T-cells were quantified using the HLA-A2:IgG dimer immediately before and 1 month after each booster administration. Patients were monitored clinically and radiographically for recurrences. Results: 188 patients were enrolled (109 VG, 79 CG). Fifty-three of the VG patients received at least one booster (B1), with 33 receiving a second booster (B2), and 20 a third booster (B3). Booster inoculations were well-tolerated with only grade 1 and 2 local and systemic toxicities. Compared to the LR at the end of the PVS (mean = 82±3mm), the mean LR increased at B1 (88±3 mm, p=0.13), B2 (94±6, p=0.02), and B3 (93±10 mm, p=0.04). Average CD8+ E75-specific T-cells did not change significantly prebooster (1.1±0.1%) compared to post-B1 (1.1± 0.1%, p=0.71) or post-B2 (1.4±0.2%, p=0.27) but did increase significantly post-B3 (2.4±0.3%, P<0.01). Additionally, the percentage of HLA-A2+ patients with significant residual immunity (defined as >0.5% CD8+E75-specific T cells) increased from pre-booster (29/43, 67%) to post-B3 (16/16, 100%; p=0.01). With 24 month clinical follow-up complete in all enrolled patients, there has been a nonsignificant decrease in recurrences observed in the VG compared to the CG (6.5% vs 13.1%, p=0.19), with no recurrences in patients who had received at least one booster inoculation by 24 months (0/40, 0%, vs 13.1% in CG, p=0.03). Conclusions: The HER2/neu E75 peptide vaccine stimulates immunity that is maintained or increased with booster inoculations in disease-free breast cancer patients. The booster inoculations are safe, with minimal toxicity. The clinical efficacy of the E75 vaccine with booster inoculations will be further evaluated in a phase III trial. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-20-01.