Immunomonitoring of triple negative breast cancer patients undergoing neoadjuvant therapy (GBG89, Geparnuevo trial)

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 inhibitor in addition to standard chemotherapy with nab-paclitaxel followed by epirubicin plus cyclophosphamide. Methods: In order to determine possible predictive and / or prognostic biomarkers, blood samples were taken before and during the different treatment phases and evaluated by multicolor flow cytometry. Results: Evaluation of the absolute cell count in the whole blood highlighted a mixed behavior of the total leukocytes, whereas there was a statistically significant reduction in the lymphocytes, particularly during the last phase of the treatment. Further dissection into the different immune populations highlighted an almost complete loss of B cells that in some patients was also accompanied by a reduction of NK cells, mostly regarding the CD16+ subset. However, the loss of CD4+ and CD8+ T cells has been less pronounced resulting in an overall enhancement of their percentages within the total lymphocytes. The different populations have also been evaluated for the expression of activation and exhaustion markers, whose behavior will be more deeply evaluated when the clinical outcome and the treatment received by the various patients will be made available. Conclusions: We expect that with such analysis possible biomarkers for the treatment of TNBC patients will be identified thus leading to better patient selection for chemo/ immune combination therapy.