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Updated: May 31, 2026
Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
Human Epidermal Growth Factor Receptor 2 Quantification Using Computational Pathology to Identify Novel Biomarkers
Ansh Kapil1, Henrik Failmezger1, Yu Fu1
1AstraZeneca Computational Pathology GmbH, Oncology Research and Development, Munich, Germany.
Purpose:
Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate approved for human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJA). Eligibility for T-DXd therapy currently relies on conventional HER2 immunohistochemistry (IHC) scoring per ASCO/CAP guidelines. Computational pathology tools such as quantitative continuous scoring (QCS) offer precise quantification of HER2 expression, enabling improved scores reflective of T-DXd's mechanism of action.
Methods:
We used HER2-QCS scoring to identify biomarker signatures in the DESTINY-Gastric01 cohort, with external validation in DESTINY-Gastric02.
Results:
QCS-derived continuous spatial proximity score (cSPS) and density of HER2-positive cells in tumor epithelium (DPC) displayed significant survival benefits for biomarker-positive versus biomarker-negative patients in the DESTINY-Gastric01 T-DXd arm (Cox regression: P < .0001). These signatures were validated in the DESTINY-Gastric02 cohort (log-rank P < .0001).
Conclusion:
Our findings indicate that cSPS and DPC are predictive of T-DXd clinical outcomes, supporting the potential future use of QCS as a quantitative approach to identify patients with GC who might benefit most from T-DXd therapy.
Insights
Quantitative continuous scoring (QCS) identifies new biomarkers for trastuzumab deruxtecan (T-DXd) therapy in gastric cancer. These biomarkers predict patient survival, improving treatment selection for HER2-positive cancers.
Area of Science:
- Oncology
- Computational Pathology
- Biomarker Discovery
Background:
- Trastuzumab deruxtecan (T-DXd) is approved for HER2-positive gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJA).
- Current eligibility for T-DXd relies on conventional HER2 immunohistochemistry (IHC) scoring.
- Quantitative continuous scoring (QCS) offers precise HER2 quantification for improved T-DXd treatment selection.
Purpose of the Study:
- To identify novel biomarker signatures predictive of T-DXd response using HER2-QCS.
- To validate these signatures in independent patient cohorts.
- To explore QCS as a quantitative method for identifying patients who may benefit from T-DXd therapy.
Main Methods:
- HER2-QCS scoring was applied to identify biomarker signatures in the DESTINY-Gastric01 cohort.
- External validation of identified signatures was performed using the DESTINY-Gastric02 cohort.
- Survival analysis using Cox regression and log-rank tests evaluated biomarker performance.
Main Results:
- QCS-derived continuous spatial proximity score (cSPS) and density of HER2-positive cells in tumor epithelium (DPC) showed significant survival benefits.
- Biomarker-positive patients demonstrated superior outcomes compared to biomarker-negative patients in the T-DXd arm (P < .0001).
- These findings were consistently validated in the DESTINY-Gastric02 cohort (log-rank P < .0001).
Conclusions:
- cSPS and DPC are significant predictors of T-DXd clinical outcomes in GC.
- QCS presents a promising quantitative approach for identifying patients likely to benefit from T-DXd.
- This study supports the potential integration of QCS into clinical practice for personalized GC treatment.
