Efficacy of Anti-HER2 Therapy with Trastuzumab Deluxecan in Uterine Carcinosarcoma Consistent with PDX-model predictions of efficacy, paving the way for the development of treatments for rare cancers.

April 10, 2023
National Cancer Center
Saitama Medical University International Medical Center
In Japanese

Presentation Points

• The efficacy of anti-HER2 therapy with trastuzumab deruxtecan was confirmed for the first time in the world for patients with unresectable, advanced or relapsed uterine carcinosarcoma, a rare and refractory cancer.
• The efficacy of trastuzumab deruxtecan was confirmed in the Patient-Derived Xenograft (PDX) model established by clinical trial participants.
• In rare cancers, where the number of patients is small and it is difficult to conduct large-scale clinical trials, the Bayesian statistics-based statistical methods used in this study and the confirmation of pharmacological effects using the PDX model are expected to be useful in the development of new treatment methods.

Summary

The National Cancer Center (President: Hitoshi Nakagama, Chuo-ku, Tokyo) Hospital (Director: Kazuaki Shimada) has conducted a phase II investigator-initiated STATICE trial at seven facilities in Japan to evaluate the efficacy of the anti-HER2 antibody-drug conjugate trastuzumab deruxtecan in patients with uterine carcinosarcoma who have HER2, a protein associated with cancer cell growth. The results showed that 54.5% of HER2-high and 70% of HER2-low expression patients showed at least 30% tumor reduction (response). The results of this study, the first in the world to demonstrate that anti-HER2 therapy may be effective in the treatment of uterine carcinosarcoma, were published on March 28, 2023 (U.S. time) in the Journal of Clinical Oncology, an American scientific journal.

At the same time, the National Cancer Center Research Institute (Director: Hiroyuki Mano), in collaboration with the Saitama Medical University International Medical Center (Director: Toshiaki Saeki, Hidaka, Saitama), established PDX (Patient-Derived Xenograft) models in which tumor tissue from a uterine carcinosarcoma patient was transplanted into combined immunodeficient mice. We established PDX models and compared the effects of trastuzumab deruxtecan in two patients who participated in the STATICE trial with the effects in the PDX model and real patients. The results showed that the PDX model and the patients had identical (effective) results, indicating that the PDX model can predict the patient’s efficacy of chemotherapy. The results of this study were published in the Clinical Cancer Research, an American scientific journal on the same day.

The results of this study indicate that trastuzumab deruxtecan may be a new treatment option for patients with uterine carcinosarcoma that expresses HER2 protein and are expected to accelerate the development of further effective treatments for rare cancers for which large-scale clinical trials are difficult to conduct.

For more information, please see the papers presented.

Papers presented at the conference

STATICE trial (Phase II investigator-initiated clinical trial)

Journal Title

Journal of Clinical Oncology

Title

Trastuzumab Deruxtecan for HER2-Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial

著者

Tadaaki Nishikawa, Kosei Hasegawa, Koji Matsumoto, Masahiko Mori, Yasuyuki Hirashima, Kazuhiro Takehara, Kazuya Ariyoshi, Tomoyasu Kato, Shigehiro Yagishita, Akinobu Hamada, Mamiko Kawasaki, Satoshi Kawashima, Sawako Tomatsuri, Yukari Nagasaka, Hiroshi Yoshida, Ryunosuke Machida, Akihiro Hirakawa, Kenji Matsumoto, Masahiko Mori, Yasuyuki Hirashima, Kazuhiro Takahara, Kazuya Ariyoshi, Tomoyasu Kato, Shigehiro Yagishita Akihiro Hirakawa, Kenichi Nakamura, Kan Yonemori

Publication date

March 28, 2023, U.S. time (March 29, Japan time)

DOI

10.1200/JCO.22.02558

URL

https://ascopubs.org/doi/full/10.1200/JCO.22.02558

Pre-clinical study of trastuzumab deruxtecan in PDX models of uterine cancer sarcoma

Journal Title

Clinical Cancer Research

Title

Co-clinical study of [fam-]trastuzumab deruxtecan (DS8201a) in patient-derived xenograft models of uterine carcinosarcoma and its association with clinical efficacy

Authors

Shigehiro Yagishita, Tadaaki Nishikawa, Hiroshi Yoshida, Daisuke Shintani, Sho Sato, Maiko Miwa, Mikiko Suzuki, Masanori Yasuda, Yusuke Ogitani, Takahiro Jikoh, Kan Yonemori, Kosei Hasegawa, Akinobu Hamada Takahiro Jikoh, Kan Yonemori, Kosei Hasegawa, Akinobu Hamada

Publication date

March 28, 2023, U.S. time (March 29, Japan time)

DOI

10.1158/1078-0432.CCR-22-3861

URL

https://doi.org/10.1158/1078-0432.CCR-22-3861

Contacts

Study Inquiries

Tadaaki Nishikawa
Medical staff, Department of Medical Oncology, National Cancer Center Hospital
E-mail: tnishika●ncc.go.jp

Shigehiro Yagishita
Senior staff scientist, Division of Molecular Pharmacology, National Cancer Center Research Institute
E-mail: syagishi●ncc.go.jp

Media Inquiries

Office of Public Relations and Planning, Department of Planning and Strategy, National Cancer Center
Email: ncc-admin●ncc.go.jp

Public Relations Office, Saitama Medical University
Email: koho●saitama-med.ac.jp