Serum HER2 extracellular domain as a predictive biomarker for trastuzumab deruxtecan treatment response in HER2-positive gastric cancer: a real-world study.
[BACKGROUND] No established predictive biomarker beyond tissue HER2 status currently exists for trastuzumab deruxtecan (T-DXd) treatment response in human epidermal growth factor receptor 2 (HER2)-pos
APA
Narita Y, Kumanishi R, et al. (2026). Serum HER2 extracellular domain as a predictive biomarker for trastuzumab deruxtecan treatment response in HER2-positive gastric cancer: a real-world study.. Therapeutic advances in gastroenterology, 19, 17562848251410771. https://doi.org/10.1177/17562848251410771
MLA
Narita Y, et al.. "Serum HER2 extracellular domain as a predictive biomarker for trastuzumab deruxtecan treatment response in HER2-positive gastric cancer: a real-world study.." Therapeutic advances in gastroenterology, vol. 19, 2026, pp. 17562848251410771.
PMID
41531803
Abstract
[BACKGROUND] No established predictive biomarker beyond tissue HER2 status currently exists for trastuzumab deruxtecan (T-DXd) treatment response in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). Serum HER2 extracellular domain (HER2 ECD) has shown potential in breast cancer; however, its clinical significance in gastric cancer remains unclear.
[OBJECTIVES] To evaluate the efficacy and safety of T-DXd in HER2-positive AGC and investigate the predictive role of serum HER2 ECD for T-DXd response.
[DESIGN] Retrospective single-institution study.
[METHODS] Data of HER2-positive AGC patients treated with T-DXd were analyzed. According to their baseline serum HER2 ECD levels, the patients were classified into high (⩾12.1 ng/mL) and low (<12.1 ng/mL) HER2 ECD groups. Tumor responses, HER2 ECD dynamics, HER2 re-biopsy status, progression-free survival (PFS), and overall survival (OS) were evaluated.
[RESULTS] Altogether, 67 patients were enrolled. The HER2 ECD data were available only for 38 patients, with 23 and 15 patients in the high and low HER2 ECD groups, respectively. The objective response rate (ORR) was significantly higher in the high HER2 ECD group (65.2%, 15/23 vs 26.7%, 4/15; = 0.045). Among the patients with immunohistochemistry (IHC) 2+/in situ hybridization (ISH+) tumors, responses were observed exclusively in the high HER2 ECD group (57.1%, 4/7 vs 0%, 0/8). Additionally, the HER2 ECD level changes post-treatment initiation also reflected tumor response, with no responses observed in the high HER2 ECD group. HER2 positivity in re-biopsy was associated with higher ORR (50.0%, 3/6 vs 25.0%, 1/4). Contrarily, the baseline HER2 ECD levels were not associated with PFS or OS.
[CONCLUSION] Baseline serum HER2 ECD may be a potential non-invasive predictor of T-DXd response in HER2-positive AGC, particularly in IHC 2+/ISH+ cases. Dynamic HER2 ECD level changes during therapy may also reflect treatment response.
[OBJECTIVES] To evaluate the efficacy and safety of T-DXd in HER2-positive AGC and investigate the predictive role of serum HER2 ECD for T-DXd response.
[DESIGN] Retrospective single-institution study.
[METHODS] Data of HER2-positive AGC patients treated with T-DXd were analyzed. According to their baseline serum HER2 ECD levels, the patients were classified into high (⩾12.1 ng/mL) and low (<12.1 ng/mL) HER2 ECD groups. Tumor responses, HER2 ECD dynamics, HER2 re-biopsy status, progression-free survival (PFS), and overall survival (OS) were evaluated.
[RESULTS] Altogether, 67 patients were enrolled. The HER2 ECD data were available only for 38 patients, with 23 and 15 patients in the high and low HER2 ECD groups, respectively. The objective response rate (ORR) was significantly higher in the high HER2 ECD group (65.2%, 15/23 vs 26.7%, 4/15; = 0.045). Among the patients with immunohistochemistry (IHC) 2+/in situ hybridization (ISH+) tumors, responses were observed exclusively in the high HER2 ECD group (57.1%, 4/7 vs 0%, 0/8). Additionally, the HER2 ECD level changes post-treatment initiation also reflected tumor response, with no responses observed in the high HER2 ECD group. HER2 positivity in re-biopsy was associated with higher ORR (50.0%, 3/6 vs 25.0%, 1/4). Contrarily, the baseline HER2 ECD levels were not associated with PFS or OS.
[CONCLUSION] Baseline serum HER2 ECD may be a potential non-invasive predictor of T-DXd response in HER2-positive AGC, particularly in IHC 2+/ISH+ cases. Dynamic HER2 ECD level changes during therapy may also reflect treatment response.
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