Second-line treatment for advanced or metastatic gastric cancer: HER2-negative, PD-L1 CPS below 5, not MSI-high

This protocol applies to patients with advanced or metastatic gastric cancer confirmed to be HER2-negative, not microsatellite instability-high (non-MSI-H), and with a PD-L1 combined positive score (CPS) below 5. These biomarker results collectively define a subpopulation where specific second-line therapeutic pathways are indicated.

Clinical context

Standard initial therapy for gastric cancer involves a platinum–fluoropyrimidine doublet. When disease progresses after that first-line chemotherapy, the combination of HER2-negative status, low PD-L1 expression, and non-MSI-H biology shapes which second-line options carry the strongest evidence base.

Treatment approach

Second-line therapy for this profile is anchored by an anti-angiogenic strategy—available as either a combination regimen or as monotherapy—backed by high-level ESMO evidence. Where the principal anti-angiogenic option is not accessible, alternative cytotoxic regimens, either as single agents or combination chemotherapy, are guideline-endorsed alternatives.

Complete regimen options, agent selection criteria, and sequencing details are available in the full 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.

Ramucirumab–paclitaxel is recommended for second-line treatment of gastric cancer [I, A; ESMO-MCBS v1.1 score: 2]. Ramucirumab monotherapy is also an option [I, B; ESMO-MCBS v1.1 score: 1].

Where ramucirumab is not available, paclitaxel, docetaxel or irinotecan monotherapy [I, A] or FOLFIRI [II, B] are recommended.

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