Adjuvant immunotherapy with the GP2 vaccine shows promise in preventing disease recurrence in patients with high-risk human epidermal growth factor receptor 2 (HER2)–positive breast cancer, especially in patients previously treated with trastuzumab.
GP2 is a HER2-derived immunogenic peptide that binds to cells that are positive for human leukocyte antigen (HLA)-A2. The vaccine is a mixture of GP2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) as an immunoadjuvant.
A phase II trial of the vaccine was conducted at The University of Texas MD Anderson Cancer Center and other institutions. The trial enrolled HLA-A2–positive patients who were cancer free after standard treatment for breast cancer; all patients had cancer that expressed the HER2 protein. The patients were at high risk for recurrence because they had lymph node–positive disease or other factors, such as high levels of HER2 expression.
Patients in the study were randomly assigned to receive adjuvant therapy with the GP2–GM-CSF vaccine or GM-CSF only. Treatment was given in an initial series of six monthly subcutaneous injections followed by four booster shots administered at 6-month intervals.
Eighty-nine patients received the GP2–GM-CSF vaccine, and 91 patients received GM-CSF only. At a median follow-up of 34 months (range, 1–60 months), disease-free survival rates were 94% and 85% for patients receiving the entire course of treatment with the GP2–GM-CSF vaccine and GM-CSF only, respectively (P = 0.17). Patients in both arms of the trial continue to be followed up for evidence of disease recurrence.
Although the difference in disease-free survival was not statistically significant, the researchers were encouraged by the finding that the 48 patients whose tumors had high levels of HER2 expression and who received the GP2–GM-CSF vaccine had a 100% disease-free survival rate.
The reason no recurrences occurred in patients whose tumors overexpressed HER2 may be that these patients received trastuzumab as part of standard therapy. According to Elizabeth Mittendorf, M.D., Ph.D., an associate professor in the Department of Surgical Oncology, trastuzumab may act as a primer for the vaccine. Trastuzumab stimulates CD4-positive T cells and initiates an antibody response. Thus, trastuzumab may act synergistically with the GP2–GM-CSF vaccine. MD Anderson is now testing this combination of immunotherapies in other clinical trials.
“We are investigating ways to prevent cancer recurrence by stimulating the immune system,” Dr. Mittendorf said. She and her colleagues presented the findings of their analysis in September at the American Society of Clinical Oncology’s 2014 Breast Cancer Symposium.
OncoLog, November-December 2014, Volume 59, Issue 11-12