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93 Sacituzumab govitecan in uterine and ovarian carcinosarcomas
  1. S Lopez1,
  2. E Perrone2,
  3. B Zeybek2,
  4. S Bellone2,
  5. A Manzano2,
  6. L Zammataro2,
  7. C Han2,
  8. G Altwerger2,
  9. R Angioli3 and
  10. A Santin2
  1. 1Università Magna Graecia, Clinical and Experimental Medicine, Catanzaro, Italy
  2. 2Yale University, Obstetrics- Gynecology- and Reproductive Sciences, New Haven, USA
  3. 3Università Campus Bio-Medico, Obstetrics and Gynecology, Rome, Italy


Objectives Carcinosarcomas (CS) are highly aggressive gynecologic malignancies containing both carcinomatous and sarcomatous elements. 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 CS cell lines and xenografts.

Methods Trop-2 expression in primary tumor cell lines and cell viability after exposure to SG, non-targeting control ADC (h679-CL2A-SN-38), and naked parental antibody hRS7 IgG were evaluated using flow-cytometry-based-assays. Antibody-dependent-cell-cytotoxicity (ADCC) against Trop-2+ and Trop-2- CS cell lines was evaluated in vitro using 4-h Chromium-release-assays. In vivo activity of SG was tested against Trop-2+ CS xenografts.

Results High expression of Trop-2 was detected in 55,5% (5 of 9) of primary CS cell lines. Primary tumors overexpressing Trop-2 were significantly more sensitive to SG when compared to control ADC (p<0.05). Both SG and parental hRS7 mediated high level of ADCC against Trop2+ CS cell lines while no cytotoxicity was detected against Trop-2 negative tumors. Importantly, SG also induced bystander killing of Trop-2 negative tumors. In vivo experiments with SG demonstrated significantly greater antitumor effects and increased survival compared to control ADC (p<0.05). SG therapy was well tolerated by the animals.

Conclusions SG demonstrated remarkable antitumor activity against biologically aggressive CS overexpressing Trop-2 and due to its hydrolizable linker may cause a significant bystander killing effect in CS with heterogenous TROP-2 expression. Clinical trials are warranted.

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