Abstract 1767P
Background
Uterine carcinosarcoma (UCS) is a rare and highly aggressive disease, which has been categorized as a subtype of high-grade endometrial cancer but not uterine sarcoma. A high clinical efficacy of a novel anti-HER2 antibody drug conjugate, trastuzumab deruxtecan (T-DXd), in HER2-positive UCS will be reported at ESMO2021 (STATICE TRIAL). Herein, we report a co-clinical study of T-DXd using patient-derived xenograft (PDX) models of patients that participated in the STATICE trial.
Methods
Tumor specimens were resected at primary surgery or biopsied at recurrence from UCS patients at Saitama Medical University International Medical Center. Those specimens were transplanted into immunodeficient mice at the National Cancer Center Research Institute. A total of seven UCS-PDXs were established, and HER2, ER, and p53 expression of PDX tumor and original tumor was assessed using Ventana I-VIEW Pathway HER2 kit (4B5, Roche, Arizona, USA), Ventana I-VIEW confirmed ER kit (SP1, Roche), and anti-p53 antibody (DO-7, Agilent, California, USA), respectively. Drug efficacy tests were conducted using six of seven PDXs in three groups: control, T-DXd 3 mg/kg, and 10 mg/kg. All drugs were administered through the tail vein on day 0.
Results
Of the six UCS-PDXs tested, two PDXs were derived from patients who were treated with T-DXd in the STATICE TRIAL. The histopathological characters of the six PDXs were well-conserved compared with each original tumor. HER2 expression was 1+ in all PDXs, and the expression of ER and p53 maintained the characteristics of the original tumors. Significant tumor shrinkage of T-DXd at both 3 mg/kg and 10 mg/kg dosing was demonstrated in four out of the six PDXs (67%), comparable to the response rate (70%) of HER2 1+ patients in STATICE TRIAL. Two patients had partial response as the best response, and the clinical effect was well replicated with significant tumor shrinkage in each UCS-PDX.
Conclusions
The UCS PDX models appear predictive of clinical efficacy and an effective preclinical evaluation platform as the results are consistent with response rates observed in the STATICE trial.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
National Cancer Center, Tokyo, Japan Saitama Medical University International Medical Center, Saitama, Japan.
Funding
Japan Agency for Medical Research and Development National Cancer Center Research and Development Fund Daiichi Sankyo Co. Ltd.
Disclosure
T. Nishikawa: Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Takeda Pharmaceutical company; Financial Interests, Personal, Advisory Board: Eisai. K. Yonemori: Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Takeda Pharmaceutical Company; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical Company; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Company; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Company. K. Hasegawa: Financial Interests, Institutional, Funding: Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo Co. Ltd. A. Hamada: Financial Interests, Institutional, Funding: Daiichi Sankyo Co. Ltd.. All other authors have declared no conflicts of interest.