Stomach cancer
ICD-10 C16 · ICD-11 2B72

First-Line Treatment for Locally Advanced Unresectable or Metastatic Gastric Cancer (HER2-Negative)

Patients with locally advanced unresectable or metastatic gastric cancer that tests negative for HER2 overexpression represent a distinct clinical group. In this setting, palliative first-line systemic therapy is the standard approach, and biomarker profiling shapes which agents are selected.

Clinical scenario

Locally advanced unresectable or metastatic gastric cancer confirmed as HER2-negative. Biomarker assessment — including PD-L1 expression and CLDN18.2 status — is integral to first-line treatment selection in this population.

Treatment approach (partial overview)

The foundation of first-line therapy is a fluoropyrimidine plus platinum-based doublet chemotherapy. Depending on the tumour's biomarker profile, additional targeted agents may be layered onto this backbone — the specific combination differs by biomarker result.

Full biomarker-stratified regimen selection and complete algorithm available in the structured protocol →
Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.5230/jgc.2025.25.e11
  1. 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.
  2. Nivolumab combined with chemotherapy is recommended for tumors with PD-L1 combined positive score (CPS) ≥5, and pembrolizumab combined with chemotherapy is recommended for tumors with PD-L1 CPS ≥1.
  3. Based on the CheckMate-649 and KEYNOTE-859 trials, nivolumab combined with chemotherapy (CAPOX or 5-FU, leucovorin, and 5-FU [FOLFOX]) and pembrolizumab combined with chemotherapy (FP or CAPOX) are currently approved as palliative first-line systemic therapy in Korea, regardless of PD-L1 status.
  4. Palliative first-line systemic therapy with zolbetuximab combined with capecitabine or fluorouracil plus oxaliplatin (CAPOX or FOLFOX) is recommended in patients with HER2-negative and CLDN18.2-positive locally advanced unresectable or metastatic gastric cancer.
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