Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas

• Published in: Oncotarget 2020-02, Vol.11 (5), p.560-570
• Main Authors: Lopez, Salvatore, Perrone, Emanuele, Bellone, Stefania, Bonazzoli, Elena, Zeybek, Burak, Han, Chanhee, Tymon-Rosario, Joan, Altwerger, Gary, Menderes, Gulden, Bianchi, Anna, Zammataro, Luca, Manzano, Aranzazu, Manara, Paola, Ratner, Elena, Silasi, Dan-Arin, Huang, Gloria S, Azodi, Masoud, Schwartz, Peter E, Raspagliesi, Francesco, Angioli, Roberto, Buza, Natalia, Hui, Pei, Bond, Heather M, Santin, Alessandro D
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.27342

Uterine and ovarian carcinosarcomas (CS) are rare cancers with poor prognosis. Sacituzumab-govitecan (SG) is a new class of antibody-drug-conjugate (ADC) targeting the human-trophoblast-cell-surface marker (Trop-2) conjugated with the active metabolite of irinotecan (SN-38). We evaluated the efficacy of SG against biologically aggressive CS. Trop-2 expression was evaluated in 10 formalin-fixed-paraffined-embedded (FFPE) CS by immunohistochemistry and 9 primary CS cell-lines by flow-cytometry. One Trop-2 low/negative (SARARK14) and two Trop-2 positive (SARARK4, SARARK9) cell-lines were tested in cell-viability assays . The antitumor activity of SG was tested in xenografts models (ie, SARARK9) with strong Trop-2 expression. Strong/diffuse staining was seen in 30% (3/10) of FFPE tumors and 33% (3/9) of primary CS cell lines. Trop-2 positive cell-lines (SARARK4, SARARK9) showed higher sensitivity to SG when compared to Trop-2 low/negative (SARARK14) cell lines. In xenografts, twice-weekly intravenous administration of SG for three weeks showed a significant tumor growth inhibition when compared to control, to ADC control and to the naked AB (p=0.004, p=0.007 and p=0.0007, respectively). SG significantly improved overall survival at 90 days when compared to control groups (p