Background: Trophoblast cell surface antigen 2 (Trop-2), encoded by the transmembrane calcium signal transducer gene, TACSTD2, is highly expressed in many cancers, including endometrial cancer (EC). Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate coupled to SN-38 (a topoisomerase 1 [Top1] inhibitor), is being evaluated in EC. Data describing TACSTD2 expression in EC are limited. We used Tempus AI, Inc., real-world data to understand TACSTD2 and TOP1 gene expression in EC and its association with other biomarkers and clinical outcomes.

Methods: Patients with metastatic uterine cancer who had longitudinal clinical and available biopsy data (whole transcriptomic and 648 gene-panel DNA-seq) in the Tempus AI, Inc., database were included. In addition, patients with uterine corpus EC from The Cancer Genome Atlas (TCGA) database were examined. For first-line (1L) survival analyses, the maximum follow-up was 12 months for real-world progression-free survival (rwPFS) and 24 months for time to next treatment or death (rwTTNTD). Gene expression comparisons were performed using Wilcoxon test, Kruskal-Wallis test, and Spearman correlation. Survival analyses to investigate TACSTD2 expression and its association with clinical outcomes were performed using Kaplan-Meier and Cox proportional hazard models.

Results: A total of 668 patients in the Tempus AI database met the inclusion criteria. TACSTD2 and TOP1 expression was similar across all molecular and major histological subtypes assessed. TACSTD2 and TOP1 expression were comparable in microsatellite instability high vs microsatellite stable biopsies, and those with mismatch repair deficient (dMMR) vs MMR proficient status. In Tempus data, TACSTD2 expression was strongly correlated with mRNA encoding Nectin-4 (r = 0.71) and moderately correlated with mRNAs encoding NaPi2b (R = 0.49) and B7-H4 (R = 0.47); all P < .05. This finding was consistent with TCGA data. In TCGA data, mutations for TACSTD2 and TOP1 were rare. In Tempus data, TOP1 mutations were rare; TACSTD2 was not part of the Tempus DNA-seq panel. TACSTD2 expression levels did not appear to be associated with rwPFS or rwTTNTD in the setting of 1L platinum chemotherapy without anti–programmed death-(ligand)1 treatment (Table).

Conclusions: TACSTD2 was broadly expressed across all EC subtypes, regardless of microsatellite or MMR status, providing rationale for evaluation of SG in all patients with EC. Frequency of TACSTD2 or TOP1 mutations was low; these mutations are not expected to be a major mechanism of primary resistance to SG. YZ and LSF contributed equally.

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