Abstract 813P
Background
Uterine carcinosarcoma (UCS) is a rare and highly malignant subtype of endometrial cancer. Paclitaxel and carboplatin therapy showed promising efficacy, but chemotherapy options are still limited. Human epidermal growth factor receptor 2 (HER2) expression was detected in 20-50% of UCS in previous studies. Hence, we conducted a clinical trial to assess the efficacy of trastuzumab deruxtecan (T-DXd) which was reported to be effective across HER2-positive cancers.
Methods
Inclusion criteria were unresectable, standard chemotherapy-refractory, and HER2-positive by immunohistochemistry (IHC) (1+ or more) UCS patients (pts). Pts were enrolled from June 2018 to June 2020 at 7 institutions in Japan. T-DXd 6.4 mg/kg was initially administered every 3 weeks until progressive disease (PD) or intolerable toxicity appeared. Following safety evaluation, the dosage was reduced to 5.4 mg/kg. The primary endpoint was overall response rate (ORR) in HER2 IHC 2+/3+ (HER2 2+/3+) on central review, and the secondary endpoints were ORR in HER2 IHC 1+ (HER2 1+) or more on central and investigators review, progression-free survival (PFS), overall survival (OS) and incidence of adverse events. The trial design was based on the Bayesian strategy for HER2 2+/3+ that we specify the minimum and maximum numbers of enrolled pts during the period and the prior distributions of ORR before beginning the trial.
Results
At data cut-off (8 Dec, 2020), 34 pts were enrolled, 22 pts with HER2 2+/3+ and 10 pts with HER2 1+ were included in the efficacy analysis. The number of responders (CR and PR) was 12 (55%), stable disease (SD) was 10 (45%) and no PD (0%) in HER2 2+/3+; therefore, it exceeded the minimum required number of responders (4 out of 22 pts). In HER2 1+ pts, the number of PR was 7 (70%), SD was 3 (30%) and no PD (0%). Interstitial lung disease (ILD) with grade (G) 1 to 3 occurred in 9 pts (27%), 4 pts (12%) with G1, 4 pts (12%) with G2, 1 pt (3%) with G3, and no G4 or G5 events were reported. The median PFS in HER2 2+/3+ was 6.2 (95% CI; 4.0-8.8) months.
Conclusions
The STATICE trial met the primary objective of ORR in HER2 2+/3+ unresectable UCS. ILD must be monitored carefully. T-DXd showed promising efficacy not only in HER2 2+/3+ but also in HER2 1+.
Clinical trial identification
Editorial acknowledgement
We thank (Mikio Mori, Tomomi Hata, Kaori Izumino, Kenta Anjo, Yoshie Shuda and Haruhiko Fukuda) from Clinical Research Support Office, National Cancer Center Hospital, Tokyo, Japan, for their advice and support in this trial. We also thank the patients, their families and all staffs of participating institutions.
Legal entity responsible for the study
National Cancer Center, Japan.
Funding
Japan Agency for Medical Research and Development, Daiichi-Sankyo Pharmaceutical Company.
Disclosure
K. Hasegawa: Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Takeda Pharmaceutical Company; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Company; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Takeda Pharmaceutical Company; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Funding: MSD. T. Nishikawa: Financial Interests, Personal, Expert Testimony: Eisai; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Takeda Pharmaceutical Company. A. Hirakawa: Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Astellas Pharma; Financial Interests, Personal, Advisory Board: Abbvie; Financial Interests, Personal, Advisory Board: Nippon Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Novartis Pharma K.K.; Financial Interests, Personal, Advisory Board: Kissei Pharmaceutical; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Nippon Shinyaku; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical; Financial Interests, Personal, Advisory Board: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: Taiho Pharmaceutical, Torii Pharmaceutical; Financial Interests, Personal, Advisory Board: Kyowa Kirin Co., Ltd.; Financial Interests, Personal, Advisory Board: Teijin Pharma; Financial Interests, Personal, Advisory Board: Fuji Pharma; Financial Interests, Personal, Advisory Board: Japan Tabacco, HEALIOS K.K; Financial Interests, Personal, Advisory Board: Life Science Institute, Inc.; Financial Interests, Personal, Advisory Board: Fujifilm Kyowa Kirin Biologics Co., Ltd. K. Matsumoto: Financial Interests, Personal, Speaker’s Bureau: Chugai; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Kyowa-Kirin; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Taiho; Financial Interests, Personal, Speaker’s Bureau: Abbie; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical Company; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Chugai; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Ono Pharmaceutical Company; Financial Interests, Institutional, Funding: ICON Japan; Financial Interests, Institutional, Funding: Novartis. A. Hamada: Financial Interests, Institutional, Funding: Daiichi Sankyo. K. Yonemori: Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Takeda Pharmaceutical Company; Financial Interests, Personal, Advisory Board: Chugai ; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Company; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Daiichi Sankyo. All other authors have declared no conflicts of interest.