First-Line Treatment of HER2-Positive Locally Advanced Unresectable or Metastatic Gastric Cancer

This protocol applies to patients with locally advanced unresectable or metastatic gastric cancer whose tumour is confirmed HER2-positive. HER2 positivity defines a distinct subgroup with a specifically tailored palliative first-line systemic strategy.

Patients present with gastric cancer that cannot be resected with curative intent — due to locally advanced extent or distant metastasis — and whose tumour testing confirms HER2 overexpression. PD-L1 combined positive score (CPS) further stratifies the recommended approach within this population.

The recommended approach is palliative first-line systemic therapy anchored by trastuzumab in combination with a fluoropyrimidine/platinum-based chemotherapy backbone. For patients with additional PD-L1 expression (CPS ≥1), an immune checkpoint inhibitor is incorporated into the trastuzumab-containing regimen. Specific agent selection, sequencing, and full dosing details are available in the complete protocol.