What are the treatment options for metastatic gastric cancer?

2026-09-15

In metastatic gastric cancer, the treatment strategy is primarily based on systemic therapies that are tailored according to molecular biomarkers (HER2, PD-L1, microsatellite instability [MSI/dMMR], and CLDN18.2). In the first-line setting, the standard backbone consists of fluoropyrimidine- and platinum-based chemotherapy combinations (such as FOLFOX, CAPOX, or SOX), which are supplemented according to biomarker status. For HER2-positive tumours, chemotherapy is combined with anti-HER2 therapy (such as trastuzumab, potentially combined with pembrolizumab); following progression, antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan are considered. In the case of HER2-negative tumours showing PD-L1 positivity or high MSI, the addition of immune checkpoint inhibitors (such as nivolumab or pembrolizumab) to chemotherapy has been shown to improve survival (particularly in cases with PD-L1 CPS ≥ 5). Furthermore, in CLDN18.2-positive cases, targeted therapy incorporating agents such as zolbetuximab represents a modern option. In the second- and subsequent-line settings, common choices include paclitaxel combined with ramucirumab (an anti-VEGFR2 antibody) or ramucirumab monotherapy, as well as irinotecan-based regimens, oral tyrosine kinase inhibitors, or trifluridine/tipiracil. In selected cases (for instance, in oligometastatic disease following an excellent response to treatment), conversion surgery may be considered, and for peritoneal metastases, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), as well as symptomatic/palliative interventions, may also be considered.

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