ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2026
Clinical impact of intratumoral HER2 heterogeneity on trastuzumab deruxtecan efficacy in patients with HER2-positive gastric cancer.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Comment on 'Clinical impact of intratumoral HER2 heterogeneity on trastuzumab deruxtecan efficacy in patients with HER2-positive gastric cancer'.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Zanidatamab vs trastuzumab with or without PD-1 blockade in HER2-positive metastatic gastric cancer: a reconstructed patient-level pooled analysis.The oncologist · 2026Article
- Spatial PK-PD mismatch in tumor-targeting antibodies and ADCs: from lesion access to pharmacologic execution.Frontiers in oncology · 2026Review
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Abstract
backgroundIntratumoral HER2 heterogeneity has been associated with poor response to trastuzumab-based chemotherapy in HER2-positive gastric cancer. However, its clinical significance in patients treated with trastuzumab deruxtecan (T-DXd) remains unclear.
methodsPatients with advanced HER2-positive gastric cancer who received T-DXd as second-line or later therapy were enrolled. HER2-positive proportion was defined as the percentage of tumor cells with immunohistochemical score ≥ 2 + in diagnostic specimens obtained before first-line therapy. The cutoff value was determined using time-dependent receiver operating characteristic analysis.
resultsForty-three patients were enrolled. Median progression-free survival (PFS) and overall survival (OS) were 4.7 and 8.1 months, respectively. With an optimal cutoff of 79%, 20 patients (47%) were in the HER2-homogeneity group and 23 (53%) in the HER2-heterogeneity group. The HER2-homogeneity group showed significantly longer PFS (6.3 vs. 3.1 months, p = 0.002) and OS (9.8 vs. 6.0 months, p = 0.006) with higher overall response rate (79% vs. 19%, p < 0.001). In Cox proportional hazards model, HER2-homogeneity was an independent prognostic factor for both PFS (hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.18–0.76, p = 0.007) and OS (HR 0.41, 95% CI 0.21–0.82, p = 0.01).
conclusionsIntratumoral HER2 heterogeneity in pre-treatment diagnostic specimens was associated with T-DXd efficacy and may represent a potential prognostic factor.
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