the latest on the E75 vaccine

[Lani]

Clin Cancer Res. 2009 Apr 7. [Epub ahead of print]
The Impact of HER2/neu Expression Level on Response to the E75 Vaccine: From U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02.

Benavides LC, Gates JD, Carmichael MG, Patel R, Holmes JP, Hueman MT, Mittendorf EA, Craig D, Stojadinovic A, Ponniah S, Peoples GE.
Authors' Affiliations: Department of Surgery, General Surgery Service, Brooke Army Medical Center, Houston, Texas; Department of Medicine, Hematology and Medical Oncology Service, and Department of Surgery, General Surgery Service, Walter Reed Army Medical Center, Washington, District of Columbia, Joyce Murtha Breast Care Center, Windber Medical Center, Windber, Pennsylvania, Department of Hematology and Medical Oncology, Naval Medical Center San Diego, San Diego, California, Cancer Vaccine Development Program, U.S. Military Cancer Institute, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
PURPOSE: HER2/neu, a source of immunogenic peptides, is expressed in >75% of breast cancer patients. We have conducted clinical trials with the HER2/neu E75 peptide vaccine in breast cancer patients with varying levels of HER2/neu expression. Vaccine response based on HER2/neu expression level was analyzed.EXPERIMENTAL DESIGN: Patients were stratified by HER2/neu expression. Low expressors (n = 100) were defined as HER2/neu immunohistochemistry (IHC) 1(+) to 2(+) or fluorescence in situ hybridization < 2.0. Overexpressors (n = 51) were defined as IHC 3(+) or fluorescence in situ hybridization >/= 2.0. Additional analyses were done stratifying by IHC status (0-3(+)). Standard clinocopathlogic factors, immunologic response (in vivo delayed-type hypersensitivity reactions; ex vivo human leukocyte antigen A2:immunoglobulin G dimer assay), and clinical responses (recurrence; mortality) were assessed.RESULTS: Low-expressor (control, 44; vaccinated, 56) versus overexpressor patients (control, 22; vaccinated, 29) were assessed. Low expressors, overexpressors, and most IHC-status vaccinated groups responded immunologically. Vaccinated low-expressor patients had larger maximum immunologic responses compared with overexpressor patients (P = 0.04), and vaccinated IHC 1(+) patients had increased long-term immune response (P = 0.08). More importantly, compared with controls, low-expressor patients had a mortality reduction (P = 0.08). The largest decrease in mortality was seen in IHC 1(+) patients (P = 0.05). In addition, a subset of overexpressor patients (n = 7) received trastuzumab before vaccination, and this combination seems safe and immunologically beneficial.CONCLUSIONS: Most patients with various levels of HER2/neu expression responded immunologically and seemed to benefit from vaccination. The low expressors, specifically IHC 1(+) patients, had more robust immunologic responses and may derive the greatest clinical benefit from the E75 vaccine.
PMID: 19351776