HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer : biomarker analyses of DESTINY-CRC01
Siena, Salvatore (Università degli Studi di Milano)
Raghav, Kanwal (The University of Texas MD Anderson Cancer Center (Houston, Estats Units d'Amèrica))
Masuishi, Toshiki (Aichi Cancer Center Hospital (Nagoya, Japó))
Yamaguchi, Kensei (The Cancer Institute Hospital of JFCR (Tokyo, Japò))
Nishina, Tomohiro (National Hospital Organization Shikoku Cancer Center (Matsuyama, Japò))
Elez, Elena (Vall d'Hebron Institut d'Oncologia)
Rodriguez, Javier (Clínica Universidad de Navarra)
Chau, Ian (The Royal Marsden NHS Foundation Trust (Sutton, Regne Unit))
Di Bartolomeo, Maria (Fondazione IRCCS Istituto Nazionale dei Tumori)
Kawakami, Hisato (Kindai University Hospital (Milà, Itàlia))
Suto, Fumitaka (Daiichi Sankyo (Basking Ridge, Regne Unit))
Koga, Makito (Daiichi Sankyo (Tokyo, Japò))
Inaki, Koichiro (Daiichi Sankyo (Tokyo, Japò))
Kuwahara, Yusuke (Daiichi Sankyo (Tokyo, Japò))
Takehara, Issey (Daiichi Sankyo (Tokyo, Japò))
Barrios, Daniel (Daiichi Sankyo (Tokyo, Japò))
Kobayashi, Kojiro (Daiichi Sankyo (Tokyo, Japò))
Grothey, Axel (West Cancer Center (Germantown, Estats Units d'Amèrica))
Yoshino, Takayuki (National Cancer Center Hospital East (Kashiwa, Japò))

Data:	2024
Resum:	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. The phase 2 trial, DESTINYCRC01, previously demonstrated durable activity of trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic colorectal cancer refractory to standard treatment. Here, the authors report the exploratory analysis of the DESTINY-CRC01 trial investigating markers of response or resistance to T-DXd.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Predictive markers ; Targeted therapies ; Cancer
Publicat a:	Nature communications, Vol. 15 (november 2024) , ISSN 2041-1723

DOI: 10.1038/s41467-024-53223-3
PMID: 39587050

12 p, 962.4 KB

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