This protocol covers patients with gastric cancer that is either locally advanced and unresectable, or has spread to distant sites, and in whom tumour testing has confirmed HER2-negative status. This biomarker distinction is central to treatment selection across all lines of therapy.
In HER2-negative disease, PD-L1 expression guides first-line decisions: an anti-PD-1 antibody combined with fluoropyrimidine/platinum-based chemotherapy is an established palliative first-line approach for patients with PD-L1-positive tumours. Microsatellite instability (MSI-H/dMMR) status is an additional biomarker that bears on treatment selection in later lines.
Palliative second-line systemic therapy for this population includes an antiangiogenic-based combination as the preferred regimen, alongside further options that depend on tumour biomarker profile.
DOI: 10.5230/jgc.2025.25.e11
Palliative first-line systemic therapy with anti-PD-1 antibody combined with fluoropyrimidine/platinum-based chemotherapy is recommended in patients with HER2-negative and PD-L1-positive locally advanced unresectable or metastatic gastric cancer.
Palliative second-line systemic therapy with ramucirumab combined with paclitaxel is recommended in patients with locally advanced unresectable or metastatic gastric cancer; however, other agents may also be considered.
Other agents, including irinotecan, docetaxel, paclitaxel can also be considered second-line options if not previously administered in the first-line treatment.
In Korea, pembrolizumab was approved in patients with several inoperable or metastatic solid tumors, including gastric cancer with MSI-H or dMMR, who have progressed following prior treatment and who have no satisfactory alternative treatment options.
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