Trophoblast Cell Surface Antigen 2 (TROP2) as a Predictive Bio-Marker for the Therapeutic Efficacy of Sacituzumab Govitecan in Adenocarcinoma of the Esophagus

Abstract

Introduction: The Trophoblast cell surface antigen 2 (TROP2) is expressed in many carcinomas and may represent a target for treatment. Sacituzumab govitecan (SG) is a TROP2–directed antibody-drug conjugate (ADC). Nearly nothing is known about the biological effectiveness of SG in esophageal adenocarcinoma (EAC). Material and Methods: We determined the TROP2 expression in nearly 600 human EAC. In addition, we used the EAC cell lines (ESO-26, OACM5.1C, and FLO-1) and a xenograft mouse model to investigate this relationship. Results: Of 598 human EACs analyzed, 88% showed varying degrees of TROP2 positivity. High TROP2 positive ESO-26 and low TROP2 positive OACM5.1C showed high sensitivity to SG in contrast to negative FLO-1. In vivo, the ESO-26 tumor shows a significantly better response to SG than the TROP2-negative FLO-1 tumor. ESO-26 vital tumor cells show similar TROP2 expression on all carcinoma cells as before therapy initiation, FLO-1 is persistently negative. Discussion: Our data suggest that sacituzumab govitecan is a new therapy option in esophageal adenocarcinoma and the TROP2 expression in irinotecan-naïve EAC correlates with the extent of treatment response by sacituzumab govitecan. TROP2 is emerging as a predictive biomarker in completely TROP2-negative tumors. This should be considered in future clinical trials.