Breast cancer vaccine may reduce risk of death

By Deena Beasley
13 april 2008 --A small trial of an experimental vaccine designed to trigger the immune system to fight breast cancer suggests that it may reduce the risk of death for most patients, U.S. military researchers said on Sunday.
The vaccine, designed to treat women with tumors that generate a protein called HER-2, has been licensed to Scottsdale, Arizona-based Apthera Inc under the brand name NeuVax.
If results from this 163-patient study are validated in a larger trial, the vaccine may offer a new therapy for the largest subset of breast cancer patients, said Linda Benavides, a resident in general surgery at Brooke Army Medical Center in San Antonio, Texas, and the study's lead researcher.
About 25 percent to 30 percent of women with breast cancer have tumors that express high levels of HER-2. Their tumors tend to grow faster and are more likely to recur than tumors that do not carry the protein.
Most of these women are currently treated with Herceptin, also known as trastuzumab, an expensive antibody-based drug made by Genentech Inc.
Researchers at Brooke Army Medical Center in San Antonio, Texas tested NeuVax in women whose tumors generated low levels of HER-2 as well as women with high levels of the protein.
At 30 months follow-up, the injected vaccine was shown to cut the risk of death for all patients by half, and in the group of patients with low-expressing HER-2 tumors, no deaths were reported. Due to the small size of the study, the survival results were not statistically significant.
The study, presented here at a meeting of the American Association for Cancer Research (AACR), also showed that cancer recurred in 10.7 percent of vaccinated low-expressors, compared with 18.2 percent of the control group.
Benavides said that a planned Phase III trial of NeuVax in more than 700 patients will test the vaccine solely in women with tumors that generate low levels of HER-2 -- a group for which immune-targeting therapy is currently unavailable.
But these breast cancer patients already have a better prognosis than women with high levels of the protein, leading to questions about whether the results can be duplicated in a larger trial.
"The surprising result is that it was the low-expressing patients who had the better outcomes ... that makes it difficult to interpret the data," said Dr. William Hait, AACR president and head of oncology research at Johnson & Johnson's Ortho Biotech unit.
Benavides said the experimental vaccine offers a "very simplistic approach," toward targeting HER-2, adding that it would be "very cheap to mass produce."

Personalized Breast Cancer Vaccine Safe in Early Trial

SAN FRANCISCO, Aug. 22 -- A personalized therapeutic breast cancer vaccine was safe and well tolerated when tested in 18 women with metastatic disease overexpressing HER-2, found researchers here.
In the phase 1 trial of the vaccine, lapuleucel-T (APC8024), there were tumor responses in one woman and disease stabilization in three, John W. Park, M.D., of the University of California San Francisco, and colleagues, reported in the Aug. 20 issue of the Journal of Clinical Oncology.
Lymphocyte proliferation and interferon gamma enzyme-linked immunospot assay detected "significant cellular immune responses specific for the immunizing antigen and HER-2 sequences were induced after treatment," they wrote.
All patients were required to have received prior treatment with trastuzumab (Herceptin), the drug that has shown a survival advantage for women with HER-2-positive tumors. Trastuzumab must have been discontinued six weeks before enrollment.
The autologous vaccine consists of peripheral blood mononuclear cells, which are obtained from patients by leukapheresis and activated in vitro with a recombinant fusion protein (BA7072 linked to GM-CSF). These activated cells including antigen-presenting cells are then re-infused intravenously into the patients.
The treatment regimen consisted of three biweekly leukaphereses and infusions. Each infusion was prepared from a single leukapheresis. The infusions were administered in escalated cell dose levels: 2 X 108, 1 X109, and 5 X 109.
Patients underwent physical examination and laboratory testing at baseline, and at two, four, eight, and 12 weeks, and at eight-week intervals thereafter.
Among the findings:
Six patients were treated at dose level 1 (2 X 108), eight patients were treated at dose level 2 (1 X109), and four patients were treated at dose level 3 (5 X 109).
Pyrexes developed in 14 patients and rigors in 11 patients.
Lapuleucel-T treatment was associated with a significant increase in proliferative response to either BA7072 (P=0.0195) or HER500 (P=0.0371) at week four and at week eight (BA7072, P=0.0029 or HER500 P=0.0137).
The median time to disease progression was 12.1 weeks (range 2.1 to 94.0+ weeks).
One woman had regression of a supraclavicular mass, which lasted for six months.
Three women had stable disease for at least a year.
"These results confirmed that this active cellular immunotherapy approach is feasible in advanced breast cancer patients who were able to receive immunologically active vaccination derived from autologous pheresis product," the investigators wrote.
The vaccine is being developed by Dendreon Corporation of Seattle, which is seeking FDA approval of a similar vaccine for prostate cancer. The prostate vaccine, set to be marketed as Provenge, was accepted for FDA fast track review in January after two clinical trials provided evidence that the vaccine stabilized the disease. But the FDA has delayed approval pending evidence that the vaccine can extend survival.
Dr. Park disclosed financial support from Dendreon, which funded the study. Primary source: Journal of Clinical OncologySource reference: Park JW et al "Treatment with Autologous Angtigen-Presenting Cells Activated With the HER-2-Based Antigen Lapuleucel-T: Results of a Phase I Study in Immunologic and Clinical Activity in HER-2-Overexpressing Breast Cancer" J Clin Oncol 2007; 25:3680-3687