Wakatsuki T, et al. - Authors attempted to investigate the clinical significance of trastuzumab in HER2-positive gastric cancer patients who had gastrectomy prior to trastuzumab-based chemotherapy. Compared to the Hetero-HER2-positive group, the median progression-free survival (PFS) and overall survival (OS) in the Homo-HER2-positive group appeared to be prominently longer. The inference drawn was that intratumoral HER2 heterogeneity could exert a robust clinical impact on the trastuzumab efficacy in patients with HER2-positive gastric cancer.

Methods

• The enrollment consisted of 28 HER2-positive gastric cancer patients who had gastrectomy prior to trastuzumab-based chemotherapy.
• A scrutiny was performed of the intratumoral HER heterogeneity using whole-tissue sections by immunohistochemistry.
• When all tumor cells overexpressed HER2 protein, the tumor was defined as homogeneously HER2 (Homo-HER2)-positive group.
• The others were defined as heterogeneously HER2 (Hetero-HER2)-positive group.

Results

• No major variation was discovered in clinicopathological features between the 2 groups.
• Substantially longer median progression-free survival (PFS) and overall survival (OS) were found in the Homo-HER2-positive group compared to those in the Hetero-HER2-positive group (PFS; 20.0 months [95% CI 17.8-22.2] vs 6.0 months [95% CI 2.3–9.7]; HR 0.11; 95% CI 0.03-0.41; p < 0.001, OS; not reached vs 14.0 months [95% CI 11.9-16.1]; HR 0.18; 95% CI 0.06-0.61; p=0.003).
• Multivariate analysis illustrated that such correlations remained significant both in PFS (HR 0.12; 95% CI 0.03-0.46, p=0.002) and OS (HR 0.21; 95% CI 0.06-0.72, p=0.013).
• In terms of response rate, there were no statistical variation between both groups.
• Nonetheless, deeper tumor shrinkage was yielded in the Homo-HER2-positive group vs Hetero-HER2-positive group (p=0.046).