Researchers at the AACR Annual Meeting 2012 presented early evidence of response in the trial, which enrolls women who are at high risk of recurrence after initial treatment and will follow them for at least three years.
The vaccine, called AE37, is a synthetic hybrid of a peptide derived from the HER2 protein, which is the target of the successful drug Herceptin. Only about 20 percent of breast cancer patients have high levels of HER2 in their tumors that are required for Herceptin to work.
"AE37 is active against HER2 at even low levels of expression of this protein, extending the population eligible for treatment to 60% of breast cancer patients or more," said principal investigator Elizabeth Mittendorf, M.D., assistant professor in MD Anderson's Department of Surgical Oncology.
The vaccine is designed to generate an immune response that will remember, recognize and destroy recurrent cancer cells expressing HER2.
All 217 women enrolled in the prospective, randomized trial, had completed standard therapy and were disease-free at the start of the trial. Of those, 109 received AE37 and the immunoadjuvant granulocyte-macrophage colony stimulating factor (GM-CSF) and 108 only GM-CSF.
All had at least some expression of HER2 in their primary tumors. The trial was blinded for the patients, but not the investigators.
"We wanted the high-risk patients, those who are at the highest risk for recurrence, so we included those patients who were node-positive or who were node-negative but had poor prognostic factors, such as ER/PR negativity," says Diane Hale, M.D., a research resident at Brooke Army Medical Center in Fort Sam Houston in San Antonio. Hale addressed a news briefing Monday and presents the research results Tuesday.
The usual three-year recurrence rate for these patients is 18-20%, Mittendorf says. At a median follow-up of 22 months, disease free survival is trending in favor of the vaccine but has not reached statistical significance.
The vaccine is followed after six months by boosters every six months four times.
Three measures indicate immune response
A skin test 48 hours after inoculation to measure delayed time hypersensitivity reaction showed 86% of those vaccinated had a physical reaction measured at 5 mm or greater while only 27% of control patients responded to that degree.
A lab test of proliferation showed a 33% rate of high responders among those receiving the vaccine, compared with 7.4% in the control group.
Finally, a measure of the number of T regulatory cells, which can undo the immune response against HER2, in about half of those enrolled showed these cells declined in 73% of patients receiving the vaccine compared with 55% of those in the control group.
An earlier phase I trial showed the vaccine to be safe, and Hale said almost all side effects are low-grade flu-like symptoms.
Follow-up continues of Phase II patients. Eric von Hofe, Ph.D., president of Antigen Express, Inc., the vaccine's developer, said the company hopes to launch a phase III clinical trial later this year.
AACR news release
HealthDay news story