Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology
- Study type
- Clinical guideline
- Study name
- NCCN Gastric v2.2025
- Design
- Clinical guideline of the US National Comprehensive Cancer Network (NCCN) with categories of evidence and consensus (1, 2A, 2B, 3); all recommendations are category 2A unless otherwise indicated
- Source
- J Natl Compr Canc Netw · 2025
In plain words
The NCCN guidelines are the main US reference for cancer treatment. According to this version, all newly diagnosed patients have an MSI/MMR test on their tumour, and in advanced disease HER2, PD-L1 and CLDN18.2 tests are also needed, because the choice of treatment (trastuzumab, immunotherapy or zolbetuximab with chemotherapy) depends on the results of these tests. In disease that can be operated on, chemotherapy before and after surgery is recommended. In patients with early stomach cancer, testing for and treating the Helicobacter pylori germ is also recommended.
Key guideline recommendations
- 2A
Universal testing for microsatellite instability (MSI) by PCR or NGS, or mismatch repair (MMR) status by immunohistochemistry, is recommended in all newly diagnosed patients. Testing for HER2, PD-L1 and claudin 18 isoform 2 (CLDN18.2) at diagnosis is recommended if advanced/metastatic disease is documented or suspected. NGS with a validated assay should be considered.
- 2A
The panel recommends testing for Helicobacter pylori infection, and eradication if positive, in all patients with early gastric cancer.
- 1 (ICI in MSI-H/dMMR: 2A)
Perioperative chemotherapy is a category 1 recommendation for patients with resectable T2 or higher tumours with any N; alternatively, preoperative/perioperative immunotherapy (checkpoint inhibitor) may be considered for selected patients with MSI-H/dMMR tumours (category 2A).
- 1 (cisplatin) / 2A (oxaliplatin)
Trastuzumab should be added to first-line chemotherapy in patients with HER2-overexpressing advanced adenocarcinoma (combination with a fluoropyrimidine and a platinum agent is preferred [category 1 for cisplatin; category 2A for oxaliplatin]).
- 1, preferred
Pembrolizumab with trastuzumab and fluoropyrimidine- and platinum-based chemotherapy is a category 1 preferred first-line option for patients with HER2-overexpressing advanced adenocarcinoma and PD-L1 CPS ≥1.
- 2A (CPS ≥1) / 1 (CPS ≥5)
In HER2-negative gastric cancer, nivolumab with fluoropyrimidine- and oxaliplatin-based chemotherapy, or pembrolizumab with fluoropyrimidine- and platinum-based chemotherapy, is a preferred first-line option for tumours with PD-L1 CPS ≥1 (in the absence of prior checkpoint inhibitor therapy or of progression on it); for CPS ≥5 these options are category 1 preferred.
- 1, preferred
Fluoropyrimidine-based chemotherapy with oxaliplatin and zolbetuximab is a category 1 preferred first-line option for patients with locally advanced unresectable, recurrent or metastatic gastric cancer with a HER2-negative, CLDN18.2-positive tumour.
- 1 (ramucirumab + paclitaxel) / 2A (T-DXd)
In the second or later line, ramucirumab with paclitaxel is a category 1 preferred option (single-agent ramucirumab: category 1, other recommended options). Trastuzumab deruxtecan is a category 2A preferred second- or later-line option for HER2-overexpressing adenocarcinoma after progression on a trastuzumab-based regimen.
Study population
Patients with gastric cancer; this excerpt (published in JNCCN) focuses on biomarker testing and treatment updates for advanced disease, including peritoneal carcinomatosis as the only site of disease and locally advanced unresectable, recurrent or metastatic disease.
Clinical significance and place in guidelines
NCCN continuously updates the full guidelines on its website (NCCN.org); this JNCCN paper is an excerpt of version 2.2025 and supersedes version 2.2022 (Ajani JA et al., J Natl Compr Canc Netw 2022;20:167–192; DOI: 10.6004/jnccn.2022.0008). This version was published before the results of MATTERHORN (perioperative durvalumab, FDA approval in November 2025) and DESTINY-Gastric04; for these treatments the current version at NCCN.org should be checked.
Limitations
This paper is only an excerpt of the full guideline and focuses on advanced disease; the full treatment algorithms for localised disease and regimen details are in the full version at NCCN.org. NCCN guidelines are written for US conditions and drug approvals and may differ from drug access in other countries.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.