Recent advances in palliative systemic therapy for locally advanced unresectable or metastatic gastric cancer: a narrative review
- Author:
Minkyu JUNG
1
Author Information
- Publication Type:Focused Issue of This Month
- From:Journal of the Korean Medical Association 2025;68(12):802-808
- CountryRepublic of Korea
- Language:Korean
- Abstract: Systemic therapy remains the cornerstone of managing advanced gastric cancer (AGC). For patients with unresectable or metastatic AGC, it is essential for extending survival and alleviating symptoms.Current Concepts: Cytotoxic chemotherapy, historically centered on fluoropyrimidines, platinum agents, taxanes, and irinotecan, continues to form the treatment foundation. More recently, targeted agents and immune checkpoint inhibitors (ICIs) have reshaped therapeutic strategies. Combination regimens incorporating nivolumab, pembrolizumab, or tislelizumab with chemotherapy have improved outcomes in HER2-negative AGC, particularly among patients with programmed cell death-ligand 1–positive or microsatellite instability-high/deficient mismatch repair tumors. Zolbetuximab, which targets CLDN18.2, has also shown clinically meaningful benefit in CLDN18.2-positive disease. In HER2-positive AGC, trastuzumab remains the therapeutic backbone, with findings from the KEYNOTE-811 trial supporting the addition of pembrolizumab to trastuzumab-based chemotherapy. In the second-line setting, ramucirumab plus paclitaxel is preferred, and trastuzumab deruxtecan provides benefit in previously treated HER2-positive patients. Later-line options include trifluridine/tipiracil, nivolumab, and trastuzumab deruxtecan.Discussion and Conclusion: The treatment landscape for AGC is rapidly evolving toward biomarker-driven precision oncology. Incorporating ICIs, targeted agents, and optimized treatment strategies has transformed management and enabled more individualized, effective, and less invasive therapeutic approaches.
