CHICAGO—A HER2 peptide vaccine called AE37 triggers strong immune responses in patients with early breast cancer, researchers reported here at the American Association for Cancer Research Annual Meeting. Preliminary data also suggest the vaccine may prolong disease-free survival, although the difference between the vaccine and control groups has not reached statistical significance in the randomized phase II trial (Abstract LB-218).
In a previous phase I study, researchers found that the AE37 peptide vaccine plus granulocyte-macrophage-stimulating factor (GM-CSF) was safe and triggered activation of CD4-positive T cells with anti-tumor activity. In the current study, investigators randomly assigned 217 women with early breast cancer to either AE37 plus GM-CSF or GM-CSF alone. All patients had completed standard therapy and were disease-free at the time of enrollment, but were at high risk of recurrence.
With a median follow-up of 22 months, 90% of patients in the vaccine arm remain disease free compared with 82.6% of the controls. When the investigators restricted their analysis to just those patients with low-HER2 expressing tumors, the trend for benefit with the vaccine was even greater, although still not statistically significant (88.6% remaining disease free compared with 69% in the control arm, p=.134).
“There is approximately a 40% reduction of recurrence for those [low-HER2] patients specifically,” said Diane F. Hale, MD, a research resident in general surgery at Brooke Army Medical Center, who presented the study. “We have seen similar benefits for low expressors in our other vaccine studies as well.” That pattern is important because it means a vaccine might be useful in a larger proportion of patients with breast cancer than currently available drugs that inhibit HER2. “Whereas Herceptin is available only to about 20% of breast cancer patients, this vaccine could be used in 50 to 60 percent of patients.”
When asked during a news conference at the meeting about the lack of statistical significance in the disease-free survival data, she noted that the current follow-up is still relatively short. “We will follow these patients to three years after therapy, so we still have time to see if there is a significant difference.” Furthermore, the Phase III trial is set to enroll 700 patients, and is designed to detect difference in clinical outcomes.
Toxicities Mostly Low Grade
All of the toxicities thus far have been low grade, with the exception of one patient who developed Grade 3 flu-like symptoms, Hale said, adding that there has not been any evidence of cardiotoxicity, as has been associated with trastuzumab treatment.
Vaccination also correlated with changes in the immune system. In a delayed-type hypersensitivity skin test, women immunized with AE37 plus GM-CSF were significantly more like to have a 5 mm or greater response compared with those who received GM-CSF alone (86% vs. 27%). Additionally, women who received the vaccine were more likely to have a substantial drop in the number of regulatory T cells, compared with women in the control group. Because regulatory T cells suppress immune responses, the decline detected after immunization suggests that the vaccine may help overcome immune tolerance.
“Their results are more impressive than I expected,” said the news conference's moderator, Olivera Finn, PhD, Distinguished and Chair of Immunology at the University of Pittsburgh School of Medicine. “I am usually very pessimistic because, to me, even early disease is still cancer that may have been there for quite a while influencing the immune system. However, my expectations have been mostly theoretical since we are just now beginning to test vaccines in early disease.
“Up until now [nearly all of the vaccines have] been tested in more advanced disease,” she continued. “From a limited number of examples, we are confirming, with data, that early is better than late. The question now will be ‘How early?’”
Unlike other immunotherapies that have gained FDA approval in recent years, which are very expensive (e.g., sipuleucel-T at $93,000 and ipilimumab at $120,000 per course), the cost of AE37 should be much more affordable, according to Eric Von Hoffe, PhD, President of Antigen Express, the company developing the vaccine: “It is fully synthetic. There are no biological reactions necessary to generate it, so it is much more cost effective than cellular-based therapies.”