Clinical Trial Results of a HER2/neu (E75) Vaccine to Prevent Recurrence in High-Risk Breast Cancer Patients

• Published in: Journal of clinical oncology Vol. 23; no. 30; pp. 7536 - 7545
• Main Authors: PEOPLES, George E, GURNEY, Jennifer M, HUEMAN, Matthew T, WOLL, Mike M, RYAN, Gayle B, STORRER, Catherine E, FISHER, Christine, SHRIVER, Craig D, IOANNIDES, Constantin G, PONNIAH, Sathibalan
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20-10-2005; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Breast Neoplasms - immunology; Breast Neoplasms - prevention & control; Cancer Vaccines - therapeutic use; CD8-Positive T-Lymphocytes - immunology; Disease Progression; Female; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Gynecology. Andrology. Obstetrics; HLA-A2 Antigen - metabolism; Humans; Immunoconjugates; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - prevention & control; Peptide Fragments - immunology; Prospective Studies; Receptor, ErbB-2 - metabolism; T-Lymphocytes, Cytotoxic - metabolism; Time Factors; Tumors; Human; Prevention; Mammary gland diseases; High risk; Relapse; Cancerology; erbB2 Gene; Clinical trial; Vaccine; Breast cancer; Malignant tumor
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2005.03.047

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 + granulocyte-macrophage colony-stimulating factor vaccine to assess safety, immunologic response, and the prevention of clinical recurrences in patients with disease-free, node-positive breast cancer (NPBC).
Fifty-three patients with NPBC were enrolled and HLA typed. HLA-A2+ patients (n = 24) were vaccinated, and HLA-A2- patients (n = 29) are observed prospectively as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence are being measured.
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 reactions to E75 postvaccination compared with controls (33 v 7 mm; P < .01). HLA-A2+ patients have been found to have larger, more poorly differentiated, and more hormonally insensitive tumors compared to 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 < .19). Median time to recurrence in the vaccinated patients was prolonged (11 v 8 months), and recurrence correlated with a weak delayed-type hypersensitivity response.
This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity seems to reduce the recurrence rate in patients with NPBC.