Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer

Abstract

Since the US FDA-approval of the first immune checkpoint inhibitor, anticytotoxic T-lymphocyte antigen-4 monoclonal antibody ipilimumab, for metastatic melanoma on 28 March 2011, another six agents have been granted use among a multitude of tumors, including renal cell cancer, Hodgkin lymphoma, urothelial carcinoma and non-small-cell lung cancer. The first anti-programmed cell death ligand-1 monoclonal antibody to receive the FDA approval, atezolizumab (Tecentriq®), has yielded promising results among international Phase III trials in triple-negative breast cancer and small-cell lung cancer, expanding the field of cancer immunotherapies. Herein, we review the pharmacodynamic and pharmacokinetic properties of atezolizumab, its safety and efficacy data from early clinical trials and summarize data from Phase III IMpassion130 trial, prompting FDA and EMA approval of atezolizumab in metastatic triple-negative breast cancer. Finally, implications for clinical use and ongoing research will be briefly discussed.

Unexpected PD‐L1 immune evasion mechanism in TNBC, ovarian, and other solid tumors by DR5 agonist antibodies

“…After a comprehensive trial in PD‐L1 + patient population, atezolizumab (anti‐PD‐L1 therapy) was recently approved for metastatic TNBC patients expressing PD‐L1 (Mavratzas et al , 2020), and since a large proportion of TNBC also express elevated DR5 levels (Forero‐Torres et al , 2010), if a bispecific PD‐L1‐DR5 antibody will further improve survival in TNBC patients need to be seen in clinical trials. Given that key factor determining tumor progression within spatiotemporal dynamics, is the infiltration and activity of cytotoxic T cells in the TME (Binnewies et al , 2018) and considering most preclinical DR5 agonist studies have relied on xenograft models lacking T cells and TME induced immunological changes in tumors (Motoki et al , 2005; Zhang et al , 2007; Camidge, 2008; Kaplan‐Lefko et al , 2010), our results support orchestration of an immune suppression by human and murine DR5 agonists.…”

TYRO3 induces anti–PD-1/PD-L1 therapy resistance by limiting innate immunity and tumoral ferroptosis

“…Tyro3-KO cells (Tyro3 −/− ) were established by transfecting 4T1-R cells using a CRISPR/Cas9 Double Nickase Plasmid (sc-423567-NIC, Santa Cruz Biotechnology). respond to immunotherapy (30). Few therapeutic options are left for those patients with TNBC who develop immunotherapy resistance.…”

Immunotherapy for Breast Cancer Treatment

“…Although the blockade of the PD-1/PD-L1 pathway by FDA has been approved, atezolizumab appears to be among encouraging methods for immunotherapy. Indeed, it could achieve only 53% response rate for metastatic breast cancer versus 33% for the placebo group [30] . Similar to the PD-L1 pathway, PD-1 inhibitors have demonstrated the modest but promising results when administrated in breast cancer patients [17,19] .…”