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

Clinical Scenario

This protocol addresses patients with locally advanced unresectable or metastatic gastric cancer whose tumours are HER2-positive. HER2 status is a key determinant of treatment selection across all lines of therapy in this setting.

Established First-Line Context

In HER2-positive locally advanced unresectable or metastatic gastric cancer, palliative first-line systemic therapy incorporating trastuzumab combined with fluoropyrimidine and platinum-based chemotherapy is the recommended starting approach.

Third-Line Approach

For patients who have progressed through prior lines of therapy, palliative third-line systemic therapy is recommended — with a preferentially indicated targeted option specifically for HER2-positive disease, alongside additional alternatives.

Complete regimen details, sequencing, and all options are in the full protocol →

Instant Access to Structured Evidence-Based Regimens

References

Palliative first-line systemic therapy with trastuzumab combined with fluoropyrimidine/platinum-based chemotherapy is recommended in patients with HER2-positive locally advanced unresectable or metastatic gastric cancer.

Palliative third-line systemic therapy is recommended in patients with locally advanced unresectable or metastatic gastric cancer. Trastuzumab-deruxtecan is preferentially recommended in patients with HER2-positive gastric cancer.

Cytotoxic agents, such as docetaxel or irinotecan, can be recommended as palliative third-line therapy.

A randomized phase III trial of trifluridine/tipiracil significantly improved OS compared to placebo (median OS, 5.7 vs. 3.6 months; HR, 0.69; 95% CI, 0.56 to 0.85; P=0.00058) in gastric cancer patients who had received at least 2 previous systemic treatments.

DOI: 10.5230/jgc.2025.25.e11 View source ↗