HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01
Abstract DESTINY-CRC01 (NCT03384940) was a multicentre, open-label, phase 2 study that investigated the safety and efficacy of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-expressing metastatic colorectal cancer (CRC). The present exploratory biomar...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53223-3 |
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| author | Salvatore Siena Kanwal Raghav Toshiki Masuishi Kensei Yamaguchi Tomohiro Nishina Elena Elez Javier Rodriguez Ian Chau Maria Di Bartolomeo Hisato Kawakami Fumitaka Suto Makito Koga Koichiro Inaki Yusuke Kuwahara Issey Takehara Daniel Barrios Kojiro Kobayashi Axel Grothey Takayuki Yoshino |
| author_facet | Salvatore Siena Kanwal Raghav Toshiki Masuishi Kensei Yamaguchi Tomohiro Nishina Elena Elez Javier Rodriguez Ian Chau Maria Di Bartolomeo Hisato Kawakami Fumitaka Suto Makito Koga Koichiro Inaki Yusuke Kuwahara Issey Takehara Daniel Barrios Kojiro Kobayashi Axel Grothey Takayuki Yoshino |
| author_sort | Salvatore Siena |
| collection | DOAJ |
| description | Abstract DESTINY-CRC01 (NCT03384940) was a multicentre, open-label, phase 2 study that investigated the safety and efficacy of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-expressing metastatic colorectal cancer (CRC). The present exploratory biomarker analysis aims to investigate relationships between biomarkers and clinical outcomes in patients with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+ and in situ hybridization [ISH] positive) Cohort A (N = 53) of DESTINY-CRC01. Higher levels of HER2 biomarkers in baseline tissue and liquid biopsies, including HER2 status (IHC/ISH), HER2/CEP17 ratio, HER2 ISH signals, HER2 H-score, plasma HER2 (ERBB2) amplification status, HER2 adjusted plasma copy number, and HER2 extracellular domain correlate with antitumor activity (indicated by objective response rate, progression-free survival, and overall survival) of T-DXd. Baseline circulating tumor DNA (ctDNA) analysis suggests antitumor activity of T-DXd in patients who had baseline activating RAS, PIK3CA, or HER2 mutations detected in ctDNA. |
| format | Article |
| id | doaj-art-26bade50fd904d768b662d98f645dae3 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-26bade50fd904d768b662d98f645dae32025-01-19T12:29:35ZengNature PortfolioNature Communications2041-17232024-11-0115111210.1038/s41467-024-53223-3HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01Salvatore Siena0Kanwal Raghav1Toshiki Masuishi2Kensei Yamaguchi3Tomohiro Nishina4Elena Elez5Javier Rodriguez6Ian Chau7Maria Di Bartolomeo8Hisato Kawakami9Fumitaka Suto10Makito Koga11Koichiro Inaki12Yusuke Kuwahara13Issey Takehara14Daniel Barrios15Kojiro Kobayashi16Axel Grothey17Takayuki Yoshino18Department of Oncology and Hemato-Oncology, Università degli Studi di Milano and Niguarda Cancer Center, Grande Ospedale Metropolitano NiguardaDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Clinical Oncology, Aichi Cancer Center HospitalThe Cancer Institute Hospital of JFCRNational Hospital Organization Shikoku Cancer CenterVall d’Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de BarcelonaMedical Oncology Department, Clinica Universidad de NavarraRoyal Marsden NHS Foundation TrustDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale TumoriKindai University HospitalDaiichi SankyoDaiichi Sankyo, Co., LtdDaiichi Sankyo, Co., LtdDaiichi SankyoDaiichi Sankyo, Co., LtdDaiichi SankyoDaiichi SankyoWest Cancer CenterNational Cancer Center Hospital EastAbstract DESTINY-CRC01 (NCT03384940) was a multicentre, open-label, phase 2 study that investigated the safety and efficacy of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-expressing metastatic colorectal cancer (CRC). The present exploratory biomarker analysis aims to investigate relationships between biomarkers and clinical outcomes in patients with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+ and in situ hybridization [ISH] positive) Cohort A (N = 53) of DESTINY-CRC01. Higher levels of HER2 biomarkers in baseline tissue and liquid biopsies, including HER2 status (IHC/ISH), HER2/CEP17 ratio, HER2 ISH signals, HER2 H-score, plasma HER2 (ERBB2) amplification status, HER2 adjusted plasma copy number, and HER2 extracellular domain correlate with antitumor activity (indicated by objective response rate, progression-free survival, and overall survival) of T-DXd. Baseline circulating tumor DNA (ctDNA) analysis suggests antitumor activity of T-DXd in patients who had baseline activating RAS, PIK3CA, or HER2 mutations detected in ctDNA.https://doi.org/10.1038/s41467-024-53223-3 |
| spellingShingle | Salvatore Siena Kanwal Raghav Toshiki Masuishi Kensei Yamaguchi Tomohiro Nishina Elena Elez Javier Rodriguez Ian Chau Maria Di Bartolomeo Hisato Kawakami Fumitaka Suto Makito Koga Koichiro Inaki Yusuke Kuwahara Issey Takehara Daniel Barrios Kojiro Kobayashi Axel Grothey Takayuki Yoshino HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01 Nature Communications |
| title | HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01 |
| title_full | HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01 |
| title_fullStr | HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01 |
| title_full_unstemmed | HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01 |
| title_short | HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01 |
| title_sort | her2 related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with her2 expressing metastatic colorectal cancer biomarker analyses of destiny crc01 |
| url | https://doi.org/10.1038/s41467-024-53223-3 |
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