HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01
Salvatore Siena, Kanwal Raghav, Toshiki Masuishi, Kensei Yamaguchi, Tomohiro Nishina, Elena Élez, Javier Rodríguez, 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
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. 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.