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.

Abstract

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 > or = 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.

• Authors: Linda C Benavides, Jeremy D Gates, Mark G Carmichael, Ritesh Patil, Ritesh Patel, Jarrod P Holmes, Matthew T Hueman, Elizabeth A Mittendorf, Dianna Craig, Alexander Stojadinovic, Sathibalan Ponniah, George E Peoples
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 8 Pg. 2895-904 (Apr 15 2009) ISSN: 1078-0432 [Print] United States
• PMID: 19351776 (Publication Type: Clinical Trial, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Cancer Vaccines
• HER-2 peptide E75 (369-377), human
• Peptide Fragments
• Receptor, ErbB-2
• Trastuzumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Breast Neoplasms (mortality, therapy)
• Cancer Vaccines (immunology, therapeutic use)
• Clinical Trials, Phase II as Topic
• Combined Modality Therapy
• Female
• Humans
• Hypersensitivity, Delayed (immunology, metabolism)
• Kaplan-Meier Estimate
• Middle Aged
• Peptide Fragments (immunology, therapeutic use)
• Receptor, ErbB-2 (biosynthesis, immunology)
• Trastuzumab