EP015/#546 In vitro and in vivo efficacy of trastuzumab deruxtecan (T-DXd) in epithelial ovarian cancer with HER2/NEU overexpression. (4th December 2022)

• Record Type: Journal Article
• Authors: Mutlu, Levent; Manavella, Diego; Bellone, Stefania; Santin, Alessandro
• Is Part Of: International journal of gynecological cancer. Volume 32(2022)Supplement 3
• Page Start: A54
• Page End: A54
• Publication Date: 2022-12-04
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2022-igcs.106
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Objectives: Epithelial ovarian cancer (EOC) has high recurrence rates, and treatment options are limited. T-DXd is a novel anti-HER2 antibody linked to the topoisomerase I inhibitor. This study aimed to determine the in vitro and in vivo efficacy of T-DXd in EOC. Methods: HER2 expression was analyzed with flow cytometry in primary high grade serous (KRCH31 and OVA3) and clear cell (OVA10 and OVA12) EOC cell lines. Cell lines were treated with T-DXd or Control antibody drug conjugate (CTL ADC). The IC50, apoptosis, bystander antitumor assays were performed. KRCH31 cells were injected into the SCID mice and animals were treated with PBS, CTL ADC or T-DXd. Results: KRCH31 and OVA10 EOC cell lines expressed HER2 by flow cytometry, OVA3 and OVA12 had negligible expression. T-DXd mean IC50 were 0.014 μg/ml and 0.017 μg/ml for KRCH31 and OVA10 cell lines, but no effect was observed in the OVA3 or OVA12 cell lines. Apoptotic cells increased to 65% and 60% in the KRCH31 and OVA10 cell lines after T-DXd. T-DXd did not show cytotoxicity on ARK4-GFP cells; however, substantial cytotoxicity was observed due to bystander antitumor activity when cocultured with KRCH31 and OVA10 cell lines (live ARK4-GFP cells 55% and 50%). Day 8 mean tumor volumes were 0.86, 0.81 and 0.43 cm 3 in PBS, CTL ADC and T-DXd treated mice, respectively (p=<0.001). Median overall survival was 15, 16.5 days and not reached in PBS, CTL ADC, T-DXd treated mice, respectively (p=0.0002). Conclusions: T-DXd showed in vitro and in vivo preclinical efficacy in HER2 overexpressing EOC. Further clinical trials are warranted.