Abstract P5-01-04: Correlation of HER2 receptor expression and in vivo activity of the HER2-targeting therapies trastuzumab deruxtecan (DS-8201a) and T-DM1 activity in a panel of breast XPDX models

作者：Alyssa Simonson, Peter Forofontov, Johnnie R Flores, Kimberly Hernandez, April B. Cabang, Amy Lang, Gladys Rodriguez, Kyriakos P. Papadopoulos, M. Beeram, Arthur Rosenthal, Brittany DeBerry, Lon Smith, Ronald Drengler, Amita Patnaik, Drew Rasco, Luis Rodriguez, Steven Abbate, Scott Ulmer, Michael J. Wick · 发表于：Cancer Research · 年份：2022 · DOI：10.1158/1538-7445.sabcs21-p5-01-04 · 研究领域：HER2/EGFR in Cancer Research、Monoclonal and Polyclonal Antibodies Research、Advanced Breast Cancer Therapies

Abstract Background: 15-20% of metastatic breast cancers are characterized by overexpression or amplification of human epidermal growth factor receptor 2 (HER2). First-line treatment for HER2-positive metastatic breast cancer includes the anti-HER2 monoclonal antibodies trastuzumab and pertuzumab in combination with chemotherapy. Second-line therapy includes T-DM1, an antibody-drug conjugate (ADC) consisting of trastuzumab conjugated to maytansinoid (DM1). Until recently, patients who progress on T-DM1 were left with few treatment options. Trastuzumab deruxtecan (DS-8201a) is an antibody-drug conjugate (ADC) consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody linked to a novel topoisomerase I inhibitor payload using a cleavable tetrapeptide-based linker and was recently approved for unresectable or T-DM1-refractory HER2+ breast cancer. In addition, DS-8201a is currently being evaluated as a treatment in breast cancers with low and medium expression of HER2. To better understand the potential for DS-8201a as a treatment in these cancer types, we evaluated this therapy in a panel of ER+/- XPDX models with differential HER2 expression. In addition, we compared DS-8201a activity to T-DM1 and benchmarked efficacy of the topoisomerase I inhibitor irinotecan in all tested models. Methods: One hundred (50ER+/50ER-) breast XPDX models were evaluated in this study. Models were established and characterized for estrogen receptor and HER2 expression by IHC and ...