HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01
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.
Authors
- Hisato Kawakami (ORCID: https://orcid.org/0000-0002-3280-4850)
- Kojiro Kobayashi (ORCID: https://orcid.org/0000-0001-6356-1671)
- Makito Koga (ORCID: https://orcid.org/0009-0005-0318-4727)
- Issey Takehara
- Koichiro Inaki (ORCID: https://orcid.org/0000-0003-1708-5533)
- Ian Chau (ORCID: https://orcid.org/0000-0003-0286-8703)
- Élena Elez (ORCID: https://orcid.org/0000-0002-4653-6324)
- Salvatore Siena (ORCID: https://orcid.org/0000-0002-2681-2846)
- Toshiki Masuishi (ORCID: https://orcid.org/0000-0002-7521-1596)
- Kanwal P. S. Raghav (ORCID: https://orcid.org/0000-0003-1311-4173)
- Yusuke Kuwahara (ORCID: https://orcid.org/0009-0000-2912-7273)
- Daniel Barrios
- Axel Grothey (ORCID: https://orcid.org/0000-0002-9341-6499)
- Fumitaka Suto (ORCID: https://orcid.org/0009-0009-5649-2650)
- Takayuki Yoshino (ORCID: https://orcid.org/0000-0002-0489-4756)
- Maria Di Bartolomeo (ORCID: https://orcid.org/0000-0002-7954-6609)
- Tomohiro Nishina (ORCID: https://orcid.org/0000-0002-4073-3757)
- Kensei Yamaguchi (ORCID: https://orcid.org/0000-0001-6887-5709)
- Javier Rodríguez
Institutions
- Universitat Autònoma de Barcelona (ES)
- Royal Marsden NHS Foundation Trust (GB)
- The University of Texas MD Anderson Cancer Center (US)
- University of Milan (IT)
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- Kindai University Hospital (JP)
- Daiichi-Sankyo (Japan) (JP)
- West Cancer Center (US)
- Aichi Cancer Center (JP)
- Clinica Universidad de Navarra (ES)
- The Cancer Institute Hospital (JP)
- Shikoku Cancer Center (JP)
- National Cancer Center Hospital East (JP)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Daiichi Sankyo (United States) (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-25
- DOI
- https://doi.org/10.1038/s41467-024-53223-3
- Citations
- 22
- Primary Topic
- Colorectal Cancer Treatments and Studies
- Type
- article
- Field-Weighted Citation Impact
- 6.22
Funders
- AstraZeneca
- Daiichi Sankyo Europe