Safety and initial clinical efficacy of a dendritic cell (DC) vaccine in locally advanced, triple-negative breast cancer (TNBC) patients (pts).
ABSTRACT
Background: Women with TNBC who do not achieve a pathologic complete response (pCR) with preoperative (preop) chemotherapy have a high risk of recurrence and death from breast cancer (BC). A high priority for clinical research is to increase the pCR rate in breast and axilla with preop therapy. Immunotherapy is an attractive strategy as human BCs can be immunogenic, and enhancing the immune effector function may augment the cytotoxic effects of standard therapies.
Methods: Following IRB-approved informed consent, 10 pts with locally advanced TNBC received standard preop dose-dense doxorubicin/cyclophosphamide (AC) followed by paclitaxel and carboplatin (TCb) chemotherapy, combined with antigen-loaded (antigens found to be overexpressed in TNBC plus control viral antigens: cyclin B1, WT1, CEF) autologous monocyte-derived DC vaccinations administered intratumorally and subcutaneously. Vaccines were given at 4 time points prior to definitive surgery, and 3 times post-surgery, pre- and post-radiation therapy. Safety is the primary study endpoint, and pCR rate in breast and axilla is a secondary endpoint. Blood was collected at baseline, prior to each vaccination, and at the end of treatment for immunologic studies. BC tissue was collected at 3 intervals during the study for biomarker evaluation.
Results: All pts received the 4 vaccines during preop chemotherapy, and 4/10 have received all 7 vaccines. 9/10 pts experienced Grade 1-2 injection site reactions. Incidence and grade of chemotherapy-related AEs were not greater than would be expected with chemotherapy alone. At the time of definitive surgery, 5 pts achieved a pCR, 3 pts had macroscopic residual disease in the breast and axillary lymph nodes, and 2 pts had residual cancer burden scores of 1. Updated clinical and immunologic biomarker evaluation is underway and data will be presented.
Conclusions: Vaccine preparation per GMP, quality control, and administration were feasible in the outpatient oncology setting. Intratumoral and subcutaneous autologous DC vaccine administration given during preop chemotherapy is safe in TNBC pts. Clinical trial information: NCT02018458