Abstract P4-06-01: Immunomonitoring of triple negative breast cancer patients undergoing neoadjuvant therapy with durvalumab - Results from the prospectively randomized GeparNuevo trial
Authors: Massa C , Schneeweiss A , Karn T , Hanusch CA , Blohmer J-U , Fasching PA , Jackisch C , van Mackelenbergh M , Marmé F , Müller V , Schem C , Stickeler E , Huober J , Weber KE , Untch M , Denkert C , Loibl S , Mueller A , Biehl K , Seliger B 
Published: May 2019

Abstract
Background: The GeparNuevo trial is a randomized, double-blind, multi-center phase II trial of neoadjuvant therapy in patients with early-stage triple negative breast cancer (TNBC) investigating the role of durvalumab, an anti-PD-L1 antibody, which blocks PD-L1 binding to PD1 and CD80, in addition to standard anthracycline/taxane based chemotherapy (Loibl S et al. ASCO 2018).
Methods: In order to determine possible predictive and / or prognostic biomarkers, blood samples were taken before and during the different treatment phases (3 or 4 time points) and evaluated by multicolor flow cytometry by monitoring the absolute cell counts of T cells, B cells and NK cells as well as the frequency, composition and functionality of different immune cell populations using a panel of 35 distinct antibodies.
Results: Overall 174 patients were randomized into the GeparNuevo study. 117 patients participated in the window phase of this study and 49 patients provided evaluable material for flow cytometric analyses for material at the above specified time points. Evaluation of the absolute cell count in the whole blood prior and after therapy highlighted a mixed behavior of the total leukocytes. Overall, there was a statistically significant reduction in the lymphocyte count, particularly during the last phase of the treatment (ECdd +/- durvalumab). Further dissection into the different immune populations highlighted an almost complete loss of B cells, which in some patients was also accompanied by a reduction of NK cells, mainly of the CD16+ subset. The loss of CD4+ and CD8+ T cells was less pronounced resulting overall in an enhancement of their percentages within the total lymphocytes. In addition, the different populations have also been evaluated for the expression of PD-L1 activation and exhaustion markers. A pre-specified analysis clearly demonstrated a specific effect of durvalumab during the window phase with mean decreases of 21.7% and 15.0 % in PDL1+ lymphocytes in the CD4+ and CD8+ subgroups, respectively (P&lt;0.001). Currently, all data generated are statistically analyzed focusing on their clinical significance in relation to the treatment received and the pathological complete remission (pCR) of these patients.
Conclusion: Using this approach we hope to identify biomarkers, which will allow a better selection of TNBC patients undergoing specific immunotherapies. Final data will be presented at the meeting.
The trial and this translational research project were funded by AstraZeneca and Celgene, Germany.
Citation Format: Massa C, Schneeweiss A, Karn T, Hanusch CA, Blohmer J-U, Fasching PA, Jackisch C, van Mackelenbergh M, Marmé F, Müller V, Schem C, Stickeler E, Huober J, Weber KE, Untch M, Denkert C, Loibl S, Mueller A, Biehl K, Seliger B. Immunomonitoring of triple negative breast cancer patients undergoing neoadjuvant therapy with durvalumab - Results from the prospectively randomized GeparNuevo trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-01.