Doctors consider immunotherapy when stomach cancer cannot be removed surgically or has spread, and the tumor’s test results support a suitable treatment. It can be part of the first treatment—not just an option after chemotherapy fails. Some patients with operable cancer can also receive it before and after surgery.
For advanced cancer, the main checks are HER2, PD-L1, and MSI/MMR, together with previous treatment and the patient’s ability to tolerate side effects. Early stomach cancer that can be removed through an endoscope usually does not need immunotherapy.
This article covers PD-1/PD-L1 checkpoint drugs within the broader field of cancer immunotherapy. The examples below use U.S. approvals; treatment availability and coverage in Japan and other countries may differ. Sources checked: October 12, 2026.
When Advanced Cancer Qualifies
| Test results | Treatment that may be considered | Conditions |
|---|---|---|
| HER2-negative and PD-L1 CPS ≥1 | Pembrolizumab plus chemotherapy | A U.S.-approved first-line option for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. |
| HER2-positive and PD-L1 CPS ≥1 | Pembrolizumab, trastuzumab, and chemotherapy | A U.S.-approved first-line option in the same advanced disease setting. |
| MSI-H or dMMR | Assessment for an immunotherapy-based regimen, including single-drug treatment in eligible patients | The U.S. pembrolizumab single-drug indication requires unresectable or metastatic disease that has progressed after prior treatment, with no satisfactory alternative treatment options. |
The pembrolizumab combinations above use fluoropyrimidine- and platinum-containing chemotherapy. The MSI-H/dMMR single-drug indication does not require a positive PD-L1 result, but its prior-treatment conditions still apply.[1]
These are examples, not a complete list of available drugs. A CPS cutoff for one regimen should not be applied to another. If chemotherapy has stopped working, the next decision also depends on whether the patient has already received a PD-1/PD-L1 drug.
When Cancer Can Be Removed
Some patients who need treatment around surgery can receive durvalumab plus FLOT chemotherapy before and after the operation, followed by durvalumab alone. The FDA approved this regimen in November 2025 for adults with resectable gastric or gastroesophageal junction adenocarcinoma, without requiring a positive PD-L1 result.[2]
FLOT contains fluorouracil, leucovorin, oxaliplatin, and docetaxel. The supporting trial involved patients with locally advanced, resectable disease; its results should not be applied to every early-stage stomach cancer.
This regimen includes surgery. The trial did not establish that immunotherapy can replace the operation or that starting durvalumab only after surgery provides the same benefit.
How Much Benefit Is Expected?
| Trial and patient group | Comparison | Reported result |
|---|---|---|
| CheckMate 649: advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma that was not HER2-positive; PD-L1 CPS ≥5 | Nivolumab plus chemotherapy versus chemotherapy alone | Median overall survival: 14.4 versus 11.1 months |
| KEYNOTE-811: advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma; PD-L1 CPS ≥1 | Pembrolizumab, trastuzumab, and chemotherapy versus trastuzumab and chemotherapy | Median overall survival: 20.1 versus 15.7 months |
| MATTERHORN: 948 patients with resectable gastric or gastroesophageal junction adenocarcinoma | Durvalumab plus FLOT versus placebo plus FLOT, given around surgery | Two-year event-free survival: 67.4% versus 58.5% |
The figures come from the initial CheckMate 649 report, the FDA’s KEYNOTE-811 analysis, and the MATTERHORN analysis published in 2025.[3][4][5]
These studies cannot rank the drugs against one another because the patients and regimens differed. Median survival is not a personal life expectancy. MATTERHORN’s 8.9-percentage-point difference concerns freedom from specified progression, recurrence, or death events—not an increase in the cure rate.
The results also cannot be transferred to NK-cell therapy: none of these trials tested natural killer cell infusions.
What Must Be Checked First?
- Pathology and stage: Confirm the cancer subtype, where it has spread, and whether surgery is possible.
- Biomarker reports: Obtain the HER2 result, PD-L1 score and scoring method, and MSI/MMR result. “PD-L1 positive” alone may not provide enough detail.
- Previous treatment: Record drug names, treatment dates, scan results, and why each treatment stopped.
- Health and medicines: Report transplant history, autoimmune disease, lung disease, previous immune-related side effects, and steroid or other immune-suppressing treatment.
MSI-H/dMMR can support consideration of immunotherapy even when PD-L1 is low. However, a positive biomarker does not guarantee a response, and confirmed progression on one PD-1 drug does not establish that switching to another will overcome resistance.[6]
Existing biopsy or surgery tissue may be enough for testing. Ask the pathology team to check before arranging another biopsy. CLDN18.2 testing may identify a separate targeted treatment option, but it does not replace the immunotherapy-related tests.
When Risks May Outweigh Benefits
Immunotherapy can trigger organ transplant rejection or worsen an autoimmune condition. Previous severe immune-related reactions and interstitial lung disease also need specialist assessment. These conditions do not all carry the same risk or automatically rule out treatment.[1]
The team will assess whether the patient can eat, wash, and dress independently, how much of the day is spent in bed or a chair, and whether weight is falling. Severe bleeding, a blockage, or an inability to eat needs prompt care rather than waiting for immunotherapy to work.
Side Effects That Need Attention
- Contact the treatment team the same day: New or worsening cough, shortness of breath, persistent diarrhea, significant abdominal pain, or blood in the stool.
- Seek prompt medical advice: Yellowing of the eyes, very dark urine, unusual weakness, excessive thirst, or frequent urination.
- Get emergency care: Severe breathing difficulty, chest pain, fainting, confusion, or heavy bleeding.
Immune-related side effects can appear after treatment ends. Tell the clinician the drug name and last treatment date. Do not start steroids without medical advice; some treatment-related hormone disorders require long-term replacement therapy.[7][1]
When Treatment Is Reviewed
Confirm the first scan date before treatment starts. Doctors assess scans alongside symptoms and blood tests; tumor marker changes alone should not decide whether treatment stops. Worsening symptoms or scans need assessment rather than an assumption of “pseudoprogression.”
Some pembrolizumab regimens for advanced cancer continue until progression, unacceptable side effects, or a maximum of 24 months. Treatment around surgery follows its own schedule.[1]
For a consultation in Japan, prepare pathology, biomarker results, recent scans, and treatment dates. The clinic’s medical records policy explains how documents are handled for translation, coordination, and provider review.