Vaccine Boosts Trastuzumab in Treatment of HER2/Neu-Positive Breast Cancer (HER2/neu

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Vaccine Boosts Trastuzumab in Treatment of HER2/Neu-Positive Breast Cancer

Last Updated: 2009-09-23 17:37:32 -0400 (Reuters Health)
By Scott Baltic
NEW YORK (Reuters Health) - Adding a specifically targeted vaccine to existing treatment with trastuzumab (Herceptin) in women with metastatic HER2/neu-positive breast cancer results in a prolonged and robust immune response against the cancer. The combination therapy is also well tolerated, U.S. researchers report online in the Journal of Clinical Oncology.
The study evaluated patients with stage IV breast cancer, most of whom had disease progression after primary treatment with chemotherapy and trastuzumab, Dr. Mary L. (Nora) Disis of the University of Washington, Seattle, told Reuters Health by e-mail.
Twenty-two patients were enrolled in the study, and 21 were treated with the HER2/neu T-helper peptide-based vaccine. Eleven women were in remission at baseline and 10 had stable disease.
Progression-free survival was better than would be expected for a well matched historical control group, Dr. Disis said. "In addition, one would expect that the median survival of this type of patient would be about two years and, in our study, at about three years of follow-up, the majority of the patients, 80%, are still alive."
Even bearing in mind the small number of patients in this study, Dr. Disis said, the data support further testing of this vaccine for advanced-stage breast cancer patients whose tumors express HER-2/neu. "We have a large phase II clinical trial ongoing here at the University of Washington to validate this promising clinical outcome."
The vaccine was designed to elicit HER2/neu-specific T-helper cell immunity. In most patients, vaccination induced or enhanced epitope spreading in association with a decrease in serum levels of human transforming growth factor beta. "Theoretically," such a decrease "could facilitate the continued augmentation and persistence of tumor-specific immunity," the authors suggest.
A related and unexpected finding was that a number of patients had already developed significant immunity to HER2/neu and other antigens before receiving the vaccine. Their pre-existing immunity was significantly boosted and maintained with vaccination.
Trastuzumab is known to be cardiotoxic, and three patients experienced a decrease in left ventricular ejection fraction, but this decrease was asymptomatic in each case.
Source:J Clin Oncol 2009.