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← Gastric Cancer

HEALTH PROFESSIONAL · SOURCE READING

Treatment Options for Stage IV, Inoperable, and Recurrent Gastric Cancer

Source: Gastric Cancer Treatment (PDQ®)–Health Professional Version, National Cancer Institute.

Source updated: February 21, 2025 · Captured 2026-09-09.

Selected source text with whitespace normalised. This Triangle page is not an NCI PDQ summary.

Context: Treatment of Stage IV, Inoperable, and Recurrent Gastric Cancer

Treatment options for stage IV, inoperable, and recurrent gastric cancer, including patients with medically or surgically unresectable disease, include a combination of cytotoxic therapies, targeted therapies, immunotherapies, and palliative locoregional therapies.

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Patients with metastatic gastric adenocarcinoma should consider undergoing testing for HER2 amplification, defective mismatch repair (dMMR) (immunohistochemistry [IHC] staining), or microsatellite instability (MSI) (polymerase chain reaction), along with programmed death ligand 1 (PD-L1) combined positive score (CPS score in the United States).

First-line palliative systemic therapy for patients with HER2-negative tumors.

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First-line palliative systemic therapy for patients with HER2-negative tumors.

Palliative chemotherapy with or without immunotherapy.

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First-line palliative systemic therapy for patients with HER2-negative tumors. › Palliative chemotherapy with or without immunotherapy.

Chemotherapy with immunotherapy: fluorouracil (5-FU) or capecitabine combined with oxaliplatin and nivolumab.

First-line palliative systemic therapy for patients with HER2-negative tumors.

Monoclonal antibody therapy with chemotherapy for patients with CLDN18.2-positive tumors.

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First-line palliative systemic therapy for patients with HER2-negative tumors. › Monoclonal antibody therapy with chemotherapy for patients with CLDN18.2-positive tumors.

Zolbetuximab plus CAPOX (capecitabine and oxaliplatin) or mFOLFOX6 (modified leucovorin [or levoleucovorin], 5-FU, and oxaliplatin).[1,2]

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First-line palliative systemic therapy for patients with HER2-negative tumors.

Triplet regimens.

First-line palliative systemic therapy for patients with HER2-negative tumors. › Triplet regimens.

5-FU combined with either epirubicin and cisplatin, etoposide and leucovorin, doxorubicin and methotrexate, leucovorin and irinotecan, or docetaxel and cisplatin or oxaliplatin.[3-9]

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First-line palliative systemic therapy for patients with HER2-negative tumors.

Doublet regimens.

First-line palliative systemic therapy for patients with HER2-negative tumors. › Doublet regimens.

A taxane (docetaxel or paclitaxel) and either cisplatin or carboplatin.

First-line palliative systemic therapy for patients with HER2-negative tumors. › Doublet regimens.

5-FU and cisplatin.

First-line palliative systemic therapy for patients with HER2-negative tumors. › Doublet regimens.

CAPOX.[10]

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First-line palliative systemic therapy for patients with HER2-negative tumors.

Single agents.

First-line palliative systemic therapy for patients with HER2-negative tumors. › Single agents.

5-FU or capecitabine.[11,12]

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First-line palliative systemic therapy for patients with HER2-negative tumors. › Single agents.

A taxane (either docetaxel or paclitaxel).

First-line palliative systemic therapy for patients with HER2-positive tumors (3+ on IHC or 2+ on IHC with a positive fluorescence in situ hybridization [FISH]).

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First-line palliative systemic therapy for patients with HER2-positive tumors (3+ on IHC or 2+ on IHC with a positive fluorescence in situ hybridization [FISH]).

Immunotherapy with chemotherapy.

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First-line palliative systemic therapy for patients with HER2-positive tumors (3+ on IHC or 2+ on IHC with a positive fluorescence in situ hybridization [FISH]). › Immunotherapy with chemotherapy.

Nivolumab with chemotherapy.

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First-line palliative systemic therapy for patients with HER2-positive tumors (3+ on IHC or 2+ on IHC with a positive fluorescence in situ hybridization [FISH]). › Immunotherapy with chemotherapy.

Trastuzumab with chemotherapy.

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Second-line palliative systemic therapy.

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Second-line palliative systemic therapy.

Palliative chemotherapy.

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Second-line palliative systemic therapy.

Ramucirumab with or without chemotherapy.

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Second-line palliative systemic therapy.

Pembrolizumab for patients with dMMR or MSI-high (MSI-H) tumors.

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Second-line palliative systemic therapy.

Trastuzumab deruxtecan for patients with HER2-positive tumors (3+ on IHC or 2+ on IHC with a positive FISH).

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Third-line palliative systemic therapy.

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Third-line palliative systemic therapy.

Trifluridine and tipiracil.

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Endoluminal laser therapy, endoluminal stent placement, or gastrojejunostomy may be helpful to patients with gastric obstruction.[13]

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Palliative radiation therapy may alleviate bleeding, pain, and obstruction.

Palliative resection is reserved for patients with continued bleeding or obstruction.

Regorafenib with nivolumab (under clinical evaluation).

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (under clinical evaluation).

Treatment with poly (ADP-ribose) polymerase (PARP) inhibitors and hepatocyte growth factor inhibitors have not shown efficacy at this time, but combination studies are under way.

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First-line palliative systemic therapy for patients with HER2-negative tumors →First-line palliative systemic therapy for patients with HER2-positive tumors (3+ on IHC or 2+ on IHC with a positive FISH) →Second-line palliative systemic therapy →Third-line palliative systemic therapy →

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Preserved source evidence · Not medical advice