Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer.

Abstract

PURPOSE:

The primary objectives of this phase I/II study were to evaluate the safety and immunogenicity of combination therapy consisting of concurrent trastuzumab and human epidermal growth factor receptor 2 (HER2)/neu-specific vaccination in patients with HER2/neu-overexpressing metastatic breast cancer.

PATIENTS AND METHODS:

Twenty-two patients with stage IV HER2/neu-positive breast cancer receiving trastuzumab therapy were vaccinated with an HER2/neu T-helper peptide-based vaccine. Toxicity was graded according to National Cancer Institute criteria, and antigen specific T-cell immunity was assessed by interferon gamma enzyme-linked immunosorbent spot assay. Data on progression-free and overall survival were collected.

RESULTS:

Concurrent trastuzumab and HER2/neu vaccinations were well tolerated, with 15% of patients experiencing an asymptomatic decline in left ventricular ejection fraction below the normal range during combination therapy. Although many patients had pre-existing immunity specific for HER2/neu and other breast cancer antigens while treated with trastuzumab alone, that immunity could be significantly boosted and maintained with vaccination. Epitope spreading within HER2/neu and to additional tumor-related proteins was stimulated by immunization, and the magnitude of the T-cell response generated was significantly inversely correlated with serum transforming growth factor beta levels. At a median follow-up of 36 months from the first vaccine, the median overall survival in the study population has not been reached.

CONCLUSION:

Combination therapy with trastuzumab and a HER2/neu vaccine is associated with minimal toxicity and results in prolonged, robust, antigen-specific immune responses in treated patients.

• Authors: Mary L Disis, Danelle R Wallace, Theodore A Gooley, Yushe Dang, Meredith Slota, Hailing Lu, Andrew L Coveler, Jennifer S Childs, Doreen M Higgins, Patricia A Fintak, Corazon dela Rosa, Kathleen Tietje, John Link, James Waisman, Lupe G Salazar
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 28 Pg. 4685-92 (Oct 01 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19720923 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Cancer Vaccines
• Peptides
• Transforming Growth Factor beta
• Receptor, ErbB-2
• Trastuzumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (adverse effects, therapeutic use)
• Breast Neoplasms (immunology, pathology, therapy)
• Cancer Vaccines (administration & dosage, immunology)
• Combined Modality Therapy
• Fatigue (etiology)
• Female
• Headache (etiology)
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Molecular Sequence Data
• Neoplasm Metastasis
• Pain (etiology)
• Peptides (chemistry, immunology)
• Receptor, ErbB-2 (chemistry, immunology)
• T-Lymphocytes (drug effects, immunology)
• Transforming Growth Factor beta (blood)
• Trastuzumab
• Treatment Outcome
• Vaccination (adverse effects, methods)