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Trastuzumab Deruxtecan for Human Epidermal Growth Factor Receptor 2–Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial
To investigate the efficacy and safety of trastuzumab deruxtecan, an antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2) with a topoisomerase I inhibitor payload, in patients with uterine carcinosarcoma (UCS) expressing HER2. PATIENTS AND METHODS: Patients with recurren...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer Health
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10414746/ https://www.ncbi.nlm.nih.gov/pubmed/36977309 http://dx.doi.org/10.1200/JCO.22.02558 |
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author | Nishikawa, Tadaaki Hasegawa, Kosei Matsumoto, Koji Mori, Masahiko Hirashima, Yasuyuki Takehara, Kazuhiro Ariyoshi, Kazuya Kato, Tomoyasu Yagishita, Shigehiro Hamada, Akinobu Kawasaki, Mamiko Kawashima, Satoshi Tomatsuri, Sawako Nagasaka, Yukari Yoshida, Hiroshi Machida, Ryunosuke Hirakawa, Akihiro Nakamura, Kenichi Yonemori, Kan |
author_facet | Nishikawa, Tadaaki Hasegawa, Kosei Matsumoto, Koji Mori, Masahiko Hirashima, Yasuyuki Takehara, Kazuhiro Ariyoshi, Kazuya Kato, Tomoyasu Yagishita, Shigehiro Hamada, Akinobu Kawasaki, Mamiko Kawashima, Satoshi Tomatsuri, Sawako Nagasaka, Yukari Yoshida, Hiroshi Machida, Ryunosuke Hirakawa, Akihiro Nakamura, Kenichi Yonemori, Kan |
author_sort | Nishikawa, Tadaaki |
collection | PubMed |
description | To investigate the efficacy and safety of trastuzumab deruxtecan, an antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2) with a topoisomerase I inhibitor payload, in patients with uterine carcinosarcoma (UCS) expressing HER2. PATIENTS AND METHODS: Patients with recurrent UCS with HER2 immunohistochemistry scores ≥1+ previously treated with chemotherapy were included. Patients were assigned to the HER2-high (immunohistochemistry score ≥2+; n = 22) or low (immunohistochemistry score of 1+; n = 10) groups for primary and exploratory analyses, respectively. Trastuzumab deruxtecan 6.4 or 5.4 mg/kg was administered intravenously once every 3 weeks until unacceptable toxicity or disease progression. Dose modification was based on the updated recommended phase II dose for breast cancer to be 5.4 mg/kg. The primary end point was the objective response rate by central review in the HER2-high group. Secondary end points included the overall response rate (ORR) in the HER2-high group by investigator assessment, ORR in the HER2-low group, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: The ORR by central review in the HER2-high and HER2-low groups were 54.5% (95% CI, 32.2 to 75.6) and 70.0% (95% CI, 34.8 to 93.3) and those by investigator assessments were 68.2% and 60.0%, respectively. The median PFS and OS in the HER2-high and HER2-low groups were 6.2 and 13.3 months and 6.7 months and not reached, respectively. Grade ≥ 3 adverse events occurred in 20 patients (61%). Grades 1-2 and 3 pneumonitis/interstitial lung disease occurred in eight (24%) and one (3%) patient, respectively. CONCLUSION: Trastuzumab deruxtecan has efficacy in patients with UCS, regardless of HER2 status. The safety profile was generally consistent with that previously reported. Toxicities were manageable with appropriate monitoring and treatment. |
format | Online Article Text |
id | pubmed-10414746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Wolters Kluwer Health |
record_format | MEDLINE/PubMed |
spelling | pubmed-104147462023-08-11 Trastuzumab Deruxtecan for Human Epidermal Growth Factor Receptor 2–Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial Nishikawa, Tadaaki Hasegawa, Kosei Matsumoto, Koji Mori, Masahiko Hirashima, Yasuyuki Takehara, Kazuhiro Ariyoshi, Kazuya Kato, Tomoyasu Yagishita, Shigehiro Hamada, Akinobu Kawasaki, Mamiko Kawashima, Satoshi Tomatsuri, Sawako Nagasaka, Yukari Yoshida, Hiroshi Machida, Ryunosuke Hirakawa, Akihiro Nakamura, Kenichi Yonemori, Kan J Clin Oncol ORIGINAL REPORTS To investigate the efficacy and safety of trastuzumab deruxtecan, an antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2) with a topoisomerase I inhibitor payload, in patients with uterine carcinosarcoma (UCS) expressing HER2. PATIENTS AND METHODS: Patients with recurrent UCS with HER2 immunohistochemistry scores ≥1+ previously treated with chemotherapy were included. Patients were assigned to the HER2-high (immunohistochemistry score ≥2+; n = 22) or low (immunohistochemistry score of 1+; n = 10) groups for primary and exploratory analyses, respectively. Trastuzumab deruxtecan 6.4 or 5.4 mg/kg was administered intravenously once every 3 weeks until unacceptable toxicity or disease progression. Dose modification was based on the updated recommended phase II dose for breast cancer to be 5.4 mg/kg. The primary end point was the objective response rate by central review in the HER2-high group. Secondary end points included the overall response rate (ORR) in the HER2-high group by investigator assessment, ORR in the HER2-low group, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: The ORR by central review in the HER2-high and HER2-low groups were 54.5% (95% CI, 32.2 to 75.6) and 70.0% (95% CI, 34.8 to 93.3) and those by investigator assessments were 68.2% and 60.0%, respectively. The median PFS and OS in the HER2-high and HER2-low groups were 6.2 and 13.3 months and 6.7 months and not reached, respectively. Grade ≥ 3 adverse events occurred in 20 patients (61%). Grades 1-2 and 3 pneumonitis/interstitial lung disease occurred in eight (24%) and one (3%) patient, respectively. CONCLUSION: Trastuzumab deruxtecan has efficacy in patients with UCS, regardless of HER2 status. The safety profile was generally consistent with that previously reported. Toxicities were manageable with appropriate monitoring and treatment. Wolters Kluwer Health 2023-05-20 2023-03-28 /pmc/articles/PMC10414746/ /pubmed/36977309 http://dx.doi.org/10.1200/JCO.22.02558 Text en © 2023 by American Society of Clinical Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | ORIGINAL REPORTS Nishikawa, Tadaaki Hasegawa, Kosei Matsumoto, Koji Mori, Masahiko Hirashima, Yasuyuki Takehara, Kazuhiro Ariyoshi, Kazuya Kato, Tomoyasu Yagishita, Shigehiro Hamada, Akinobu Kawasaki, Mamiko Kawashima, Satoshi Tomatsuri, Sawako Nagasaka, Yukari Yoshida, Hiroshi Machida, Ryunosuke Hirakawa, Akihiro Nakamura, Kenichi Yonemori, Kan Trastuzumab Deruxtecan for Human Epidermal Growth Factor Receptor 2–Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial |
title | Trastuzumab Deruxtecan for Human Epidermal Growth Factor Receptor 2–Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial |
title_full | Trastuzumab Deruxtecan for Human Epidermal Growth Factor Receptor 2–Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial |
title_fullStr | Trastuzumab Deruxtecan for Human Epidermal Growth Factor Receptor 2–Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial |
title_full_unstemmed | Trastuzumab Deruxtecan for Human Epidermal Growth Factor Receptor 2–Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial |
title_short | Trastuzumab Deruxtecan for Human Epidermal Growth Factor Receptor 2–Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial |
title_sort | trastuzumab deruxtecan for human epidermal growth factor receptor 2–expressing advanced or recurrent uterine carcinosarcoma (ncch1615): the statice trial |
topic | ORIGINAL REPORTS |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10414746/ https://www.ncbi.nlm.nih.gov/pubmed/36977309 http://dx.doi.org/10.1200/JCO.22.02558 |
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