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51 In vitro and in vivo activity of sacituzumab govitecan, in ovarian cancer
  1. E Perrone1,
  2. S Lopez1,
  3. B Zeibek1,
  4. S Bellone1,
  5. L Zammataro1,
  6. A Manzano1,
  7. E Bonazzoli1,
  8. P Manara1,
  9. G Scambia2 and
  10. A Santin1
  1. 1Yale University, Obstetrics- Gynecology- and Reproductive Sciences, New Haven, USA
  2. 2Universita’ Cattolica del Sacro Cuore, Department of Women’s and Children’s Health, Rome, Italy


Objectives Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Sacituzumab govitecan (SG) is a novel antibody-drug-conjugate (ADC) targeting trophoblast-antigen-2 (Trop-2), a cell surface glycoprotein highly expressed in many epithelial tumors, to deliver SN-38, the active metabolite of irinotecan. This study aimed to evaluate the efficacy of SG in primary EOC cell lines and xenografts.

Methods Trop-2 expression was evaluated in 90 formalin-fixed-paraffin-embedded (FFPE) tumors and 9 primary tumor cell lines by immunohistochemistry and flow cytometry, respectively. Trop-2 expression and cell viability after exposure to SG in primary tumor cell lines, non-targeting control-ADC (h679-CL2A-SN-38), and SG-parental antibody hRS7 IgG wereevaluated using flow-cytometry-based-assays. Antibody-dependent-cell-cytotoxicity (ADCC) against Trop-2+ and Trop-2- EOC cell lines was evaluated in vitrousing 4-h Chromium-release-assays. In vivoactivity of SG was tested againstTrop-2+ EOC xenografts.

Results Moderate-to-strong staining was seen in 47% (42/90) of ovarian tumors while 89% (8/9) of the primary EOC cell lines overexpressed Trop-2. EOC overexpressing Trop-2 were significantly more sensitive to SG compared to control ADC (p<0.05). Both SG and hRS7 mediated high ADCC activity only against Trop2+ cell lines. SGalso induced bystander killing of Trop-2- tumor cells. In vivoexperiments with SG in EOC xenografts demonstrated greater antitumor effects and increased survival compared to ADC controls (p<0.05). SG was well tolerated by the animals.

Conclusions SG has shown remarkable preclinical activity against biologically aggressive EOC and it is endowed with significant bystander effect against tumors with heterogenous TROP-2 expression. Clinical trials are warranted.

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