Abstract ES9-2: Updates on immunotherapy for TNBC
Authors: Adams S 
Published: May 2019

Abstract
Immunotherapeutic strategies have revolutionized the treatment of cancer. Immune checkpoint blockade (ICB) agents such as inhibitors of programmed cell death receptor-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been FDA-approved for the treatment of various tumors.
While breast cancers have previously been considered immunologically quiescent compared with other tumor types, recent investigations underscore the immunogenicity of some breast tumors. Triple negative breast cancers (TNBCs) in particular, have the highest rates of tumor-infiltrating lymphocytes (TILs) compared with other subtypes at diagnosis. TILs are indicative of a pre-existing anti-tumor immune response which carries a better prognosis in patients with early TNBC, at least in part due to a better response to conventional cancer therapies. It has been demonstrated that TILs correlate with pathologic complete response (pCR) after neoadjuvant chemotherapy (Denkert et al, Lancet Oncol 2018). The survival benefit associated with TIL in early TNBC is remarkable with a 10% increase in TIL correlating with a 19% reduction in risk of death in trials of adjuvant chemotherapy (Adams et al, J Clin Oncol 2014). These advances ignited the studies of ICB in TNBC with the goal to harness the anti-tumor immune response to improve patient outcomes.
Initial Phase I/II trials in metastatic TNBC showed proof of principle that durable responses could be achieved with ICB monotherapy, but also highlighted the need to develop rational combinations. ICB agents address one important step by which the T-cell response can be blunted, counteracting PD-L1 expressed in the tumor microenvironment in an effort to avoid immune destruction. However, as depicted in the Cancer Immunity Cycle, which manages the delicate balance between the recognition of nonself and the prevention of autoimmunity (Chen et al, Immunity 2013), there are multiple steps required for an effective immune response. Released tumor antigens must be presented in the context of major histocompatibility complexes (MHC) on activated antigen presenting cells to prime an efficient T cell response. Activated T cells must then traffic to the tumor site, infiltrate into the tumor, recognize, and kill tumor cells. Different therapeutic strategies including chemotherapy and radiotherapy are currently being studied as combination partners due to their potential of inducing an immunogenic cell death (Galluzzi et al, Nat Rev Immunol 2017).
Recently the first positive phase 3 chemo-immunotherapy study was reported in metastatic TNBC (Schmid et al, ESMO 2018). Impassion130, a global, randomized, double-blind trial of nab-paclitaxel with or without atezolizumab in front-line metastatic TNBC, met its co-primary progression-free survival (PFS) endpoint in the intent-to-treat as well as the PD-L1+ population, with clinically meaningful overall survival (OS) benefit seen at interim OS analysis in PD-L1+ patients. Additional phase 3 trials of ICB in TNBC are ongoing in the adjuvant, neoadjuvant and metastatic setting.
Citation Format: Adams S. Updates on immunotherapy for TNBC [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 ES9-2.