First-Line Treatment for Advanced or Metastatic Gastric Cancer: HER2-Negative, Not MSI-High, PD-L1 CPS Below 5

This protocol addresses first-line systemic treatment for patients with advanced or metastatic gastric cancer defined by a specific biomarker profile. Identifying this subgroup — HER2-negative, not microsatellite instability-high, and PD-L1 combined positive score below 5 — is essential to selecting the evidence-based treatment approach.

Clinical scenario

Advanced or metastatic gastric cancer with all three biomarker characteristics present:

Treatment approach

Standard first-line treatment in this setting is chemotherapy built around a platinum–fluoropyrimidine doublet. The choice of agents within this doublet is guided by individual patient factors — including tolerability — with different combinations considered depending on the clinical picture.

The complete regimen, agent selection guidance, and sequencing details are available in the full structured protocol below.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1016/j.annonc.2022.07.004

Standard first-line ChT for gastric cancer is a platinum–fluoropyrimidine doublet.
First-line ChT with a platinum and fluoropyrimidine is recommended. Oxaliplatin is preferred, especially for older patients [I, A].
Recommended fluoropyrimidines are intravenous 5-FU, oral capecitabine or oral S-1.
Irinotecan–5-FU can be considered an alternative option for patients who do not tolerate platinum compounds [II, B].

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