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

SIMPLE SUMMARY: The trophoblast cell surface antigen 2 (TROP2) is a protein produced by many carcinomas. Sacituzumab govitecan (SG) is a drug consisting of an antibody that binds to TROP2 on the tumor cell when TROP2 is present and is taken up into the cell interior after binding. The antibody is coupled with a cytotoxic substance (SN38) that is released inside the cell after uptake. As a result, a lethal dose of SN38 acts specifically in the tumor cell while having a small systemic effect, reducing the extent of side effects. We can show here that TROP2 is formed in nearly 90% of esophageal adenocarcinomas (EAC) and that sacituzumab govitecan is also effective in EAC. We can show that efficacy is dependent on the presence of TROP2 on the cancer cell - complete absence of TROP2 is associated with poor response rate to SG. We therefore advocate determining TROP2 at the protein level prior to therapy. Suitable immunohistochemical antibodies for routine testing exist. 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.