San Francisco, CA—A new GP2 peptide vaccine was safe and reduced the rate of breast cancer recurrence in women with high-risk breast cancer in a phase 2 clinical trial. The vaccine was particularly effective in reducing recurrence in women with HER2 overexpression, reported Elizabeth A. Mittendorf, MD, PhD, Assistant Professor of Surgical Oncology, M.D. Anderson Cancer Center, Houston, at the 2014 Breast Cancer Symposium.
The vaccine is delivered in the adjuvant setting, after the completion of standard-of-care therapy, including trastuzumab (Herceptin) where appropriate, along with the immunoadjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) to help stimulate an immune response.
“Peptide vaccines have the benefit of being easy to construct and manufacture on a large scale, they’re inexpensive, and, very importantly, they are ‘off-the-shelf’ therapy,” said Dr Mittendorf.
GP2 is a HER2-derived HLA-A2–positive, restricted immunogenic peptide designed to stimulate CD8+ cytotoxic T lymphocytes to recognize breast cancer cells with HER2 expression, said Erika J. Schneble, DO, coinvestigator of the study and a general surgery resident at San Antonio Military Medical Center, TX.
In the multicenter phase 2 trial, 180 women with HLA-A2–positive, node-positive or high-risk node-negative breast cancer with any level of HER2 expression who were rendered disease-free with standard-of-care therapy were randomized to receive GP2 plus GM-CSF or GM-CSF alone. HER2 overexpression was present in 57% of patients who received the vaccine and in 55% of patients in the control group.
Only 1 grade 3 local and systemic toxicity was reported in the vaccine group. “The toxicities are mostly grade 1 local and systemic toxicities that match the control arm, suggesting that these toxicities are due to just the immunoadjuvant GM-CSF,” said Dr Schneble. Approximately 70% of patients in each arm had grade 1 local toxicities. In all, 70% of patients in the GM-CSF–alone arm and 60% of patients in the vaccine plus GM-CSF arm had grade 1 systemic toxicity.
After a median follow-up of 34 months, the disease-free survival (DFS) rate was 88% with the GP2 vaccine and 81% in the control group (P = .428). Excluding the patients who had a recurrence during their primary vaccination series or who had a second malignancy, the DFS rate was 94% with the vaccine versus 85% in the control group (P = .168).
“After completion of the primary vaccine series, there have been no recurrences in the HER2 3+ population,” said Dr Schneble. “This suggests a possible synergy with trastuzumab. All [HER] 3+ patients received trastuzumab as their standard-of-care therapy.”
The concurrent use of trastuzumab and the GP2 vaccine may address the early recurrences, Dr Mittendorf said. A phase 1 clinical trial of concurrent use showed the combination to be safe, with no increases in toxicities. A phase 2 trial examining combination immunotherapy with trastuzumab and a CD8–positive T-cell–eliciting vaccine is expected to begin enrolling patients.
