Abstract P5-16-03: Phase II study of autologous dendritic cell vaccination in patients with HER2 negative breast cancer combined with neoadjuvant chemotherapy
Authors: Castillo A , Salgado E , Inoges S , Arevalo E , Castañon E , López Díaz de Cerio A , Sola JJ , Pina L , Nuñez J , Rodriguez-Spiteri N , Espinós J , Aramendia JM , Fernandez Hidalgo OA , Santisteban M 
Published: August 2014

Abstract
Background The limited efficacy of neoadjuvant schedules to obtain pCR in breast cancer together with a prompt relapse of triple negative breast cancers has opened up the development of new strategies involving the immune system, which is essential in cancer control. We have elaborated an autologous vaccine with dendritic cells loaded with patients' own tumor antigens. Based on the synergistic effect between immunotherapy and chemotherapy our hypothesis is that the combination of both strategies could improve pCR with an excellent tolerance and could increase DFS and OS.
Methods Two centers are enrolling patients from February 2011. Twenty-one patients with stage II-III HER2 negative breast cancer have started on sequential neoadjuvant chemotherapy based on dose dense antracyclines (E 100mg/m2 and C 600 mgr/m2) × 4 cycles plus GM-CSF followed by taxanes (DOC 75–100 mgr/m2) × 4 cycles plus vaccination. Vaccine calendar was started after the 4th EC and alternated with taxane schedule and after chemotherapy up to a maximum of a 2 year-period. SNB biopsy was performed before neoadjuvant chemotherapy. pCR in the breast and the axilla is the main endpoint, measured by Miller&Paine classification. Data were analyzed using SPSS and alpha was set at 0.05 (two-tailed). We have compared these results in the vaccinated cohort (V) with our historic cohort (C) of 19 patients treated in the same way but without the vaccine.
Results Both cohorts (V and C) were well balanced for age, histologyc type, differentiation grade, Ki67&gt;15%, tumor size ≤ 5 cm, stage and expression of hormone receptors. All patients except one in the vaccine cohort achieved 8 cycles of chemotherapy. According to grade ¾ toxicities we did not find significant differences except for hand-foot syndrome in the V cohort (19% vs 0%; p = 0.04) and vomiting in the C cohort (0% vs 21%; p = 0.02). Lymphopenia was the most common adverse event (81% in V vs 89.5% in C; p = 0.45). Other toxicities were anemia (0% vs 5.3%; p = 0.28), thrombopenia (0% vs 10% p = 0.12), leukopenia (9.5% vs 15.8% p = 0.55) and neutropenia (14% vs 21%, p = 0.57). Gastrointestinal toxicity was similar in both groups: mucositis (0% vs 5.3%, p = 0.28); gastritis (5% in both cohorts), nausea (19% vs 16%, p = 0.78), diarrhea (5% in both cohorts), constipation (0% vs 15% in C, p = 0.06). Myalgias were seen in 19% in V vs 11% in C (p = 0.45). We did not see any local grade ¾ toxicity related to the intradermal vaccines. Regarding efficacy data, clinical complete response by MRI was shown in 38% in the V as compared to 16% in the C (p = 0.06). Breast-conserving surgery was more common in the V cohort (62% vs 53%, p = 0.55). Total pCR (T plus N) was superior with the addition of the vaccine (24% vs 5% p = 0.014). Moreover in three more patients in the V group we find isolated tumor cells in the breast (Titc).
Conclusions The addition of autologous dendritic cell vaccines to neoadjuvant chemotherapy significantly increased the rate of pathological complete responses among patients with HER2-negative breast cancer. Vaccination does not seem to add any toxicity to the schedule.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-16-03.