PD-L1-high gastric cancer
PD-L1-high gastric cancer expresses the immune checkpoint protein PD-L1 on tumour and immune cells, and this is the group in which nivolumab or pembrolizumab added to chemotherapy clearly extends life. The benefit shrinks as the score falls, so regulators now restrict the antibodies to tumours with at least some PD-L1 expression.
Overview
PD-L1 in stomach cancer is scored with the combined positive score, the number of PD-L1-staining tumour cells, lymphocytes and macrophages divided by the number of viable tumour cells, using the 28-8 or 22C3 antibody. Epstein-Barr virus-positive tumours, about one in eleven, express PD-L1 heavily and respond best of all; microsatellite-unstable tumours do too. Scores of 5 or above with the 28-8 assay and 1 or above with 22C3 have become the practical thresholds, and the two assays are not perfectly interchangeable.
CheckMate 649 (Lancet 2021) randomised HER2-negative advanced gastric, junctional and oesophageal adenocarcinoma to nivolumab plus oxaliplatin-fluoropyrimidine chemotherapy or chemotherapy alone; in the combined positive score 5 or above group median overall survival rose from 11.1 to 14.4 months, and in all randomised patients from 11.6 to 13.8 months, with the gain concentrated in tumours with higher scores and persisting at five years. KEYNOTE-859 (Lancet Oncology 2023) did the same with pembrolizumab, improving median survival from 11.5 to 12.9 months overall, from 11.4 to 13.0 months in score 1 or above and from 11.8 to 15.7 months in score 10 or above. Chinese trials with tislelizumab and sintilimab followed the same pattern.
Regulators drew different lines. The FDA first approved nivolumab in 2021 regardless of PD-L1 and pembrolizumab in 2023, then in 2025 narrowed both to tumours with a combined positive score of 1 or above after its advisory committee found no benefit below that score; the European label requires a score of 5 for nivolumab. In resectable disease MATTERHORN added durvalumab to perioperative FLOT and improved event-free survival in all patients, PD-L1 status notwithstanding, so the biomarker matters most in the metastatic setting.
State of the art
- The combined positive score is one of the few checkpoint biomarkers with a clear dose-response across trials.
- Durvalumab with FLOT brought immunotherapy into curative-intent treatment without needing the biomarker.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Nivolumab and pembrolizumab with chemotherapy are the first-line standard for PD-L1-expressing HER2-negative disease, with five-year survivors in CheckMate 649.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowBowel perforation
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
- Check before combiningFood and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
- Good to knowImmune-related endocrinopathies (thyroiditis, hypophysitis)
Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.
- Good to knowPeripheral neuropathy (chemotherapy-induced)
Nerve damage from chemotherapy that causes numbness, tingling and pain in the hands and feet, and sometimes weakness or hearing loss. It builds up with each dose, can be permanent, and is the main reason oxaliplatin, taxanes and vincristine have to be stopped or reduced.
See all on the product pages:CAPOX (capecitabine, oxaliplatin)DurvalumabFLOT (5-FU, leucovorin, oxaliplatin, docetaxel)FOLFOX (5-FU, leucovorin, oxaliplatin)NivolumabPaclitaxel / nab-paclitaxelPembrolizumabRamucirumab·Printable cards in the navigator
Anatomy and lymph node drainage
- Upper and middle oesophagus (squamous)
- Lower oesophagus and junction (adenocarcinoma)
- Cardia and fundus
- Body (diffuse or intestinal type)
- Antrum and pylorus
- Muscle wall (GIST)
- Nodes: perigastric (greater and lesser curve)
- Nodes: coeliac and hepatic
- Nodes: mediastinal
- Nodes: cervical (upper oesophagus)
Squamous cancers sit in the upper and middle oesophagus, adenocarcinomas at the junction and in the stomach; the stomach wall also gives rise to GIST from its pacemaker cells.
- Upper and middle oesophagus (squamous)
- Lower oesophagus and junction (adenocarcinoma)
- Cardia and fundus
- Body (diffuse or intestinal type)EBV-positive gastric cancer (PD-L1 high, immunotherapy-responsive)
- Antrum and pylorus
- Muscle wall (GIST)
- perigastric (greater and lesser curve)
- coeliac and hepatic
- mediastinal
- cervical (upper oesophagus)
Same organ: Gastric & gastro-oesophageal junction cancer, HER2-positive gastric cancer, Claudin 18.2-positive gastric cancer, Microsatellite-unstable (MSI-high) gastric cancer, Early gastric cancer, Oesophageal squamous cell carcinoma, Oesophageal and junctional adenocarcinoma, Oesophageal cancer, Gastrointestinal stromal tumour (GIST), KIT exon 11-mutant GIST, PDGFRA D842V-mutant GIST, Imatinib-resistant GIST
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Roughly six in ten advanced gastric adenocarcinomas have a PD-L1 combined positive score of 1 or above and about half score 5 or above; the higher the score, the larger the survival gain from adding a PD-1 antibody to chemotherapy.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Nivolumab with FOLFOX or CAPOX (CheckMate 649) or pembrolizumab with platinum-fluoropyrimidine chemotherapy (KEYNOTE-859).
PD-1 antibody with chemotherapy is permitted in the United States and offered with a smaller expected gain; chemotherapy alone or zolbetuximab where claudin 18.2 is positive.
Perioperative FLOT with durvalumab (MATTERHORN), given irrespective of PD-L1 score.
Ramucirumab with paclitaxel (RAINBOW); no established role for continued PD-1 blockade.
Subtypes & biomarkers
top- PD-L1 CPS 10 or above (largest benefit)
- PD-L1 CPS 5 or above (nivolumab label in Europe)
- PD-L1 CPS 1 to 4 (smaller benefit)
- EBV-positive gastric cancer (PD-L1 high, immunotherapy-responsive)
- PD-L1-negative (chemotherapy alone unless another target is present)
- PD-L1 combined positive score (28-8 or 22C3 assay)
- Epstein-Barr virus in situ hybridisation
- Microsatellite instability and mismatch repair (overlapping responders)
- HER2 (must be negative for this pathway)
- Claudin 18.2 (competing first-line target)
How often this target appears
- 2017KEYNOTE-059 and ATTRACTION-2: PD-1 antibodies active in late-line gastric cancer
- 2021CheckMate 649: nivolumab plus chemotherapy extends survival; FDA approval
- 2023KEYNOTE-859: pembrolizumab plus chemotherapy extends survival
- 2025FDA restricts first-line PD-1 antibodies to PD-L1 CPS 1 or above; MATTERHORN positive with durvalumab and FLOT
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 9 changes by month →- 2026-09-17This recordPD-L1-high gastric cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2025Trial resultMATTERHORNMATTERHORN reported
EFS HR 0.
- 2025MilestoneMATTERHORNFDA restricts first-line PD-1 antibodies to PD-L1 CPS 1 or above; MATTERHORN positive with durvalumab and FLOT
A milestone in how this cancer is treated.
- 2023Trial resultKEYNOTE-859KEYNOTE-859 reported
OS HR 0.
- 2023MilestoneKEYNOTE-859KEYNOTE-859: pembrolizumab plus chemotherapy extends survival
A milestone in how this cancer is treated.
- 2021MilestoneCheckMate 649CheckMate 649: nivolumab plus chemotherapy extends survival; FDA approval
A milestone in how this cancer is treated.
What is in development for PD-L1-high gastric cancer, drawn from the whole corpus: 6 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Drugs in phase 3 · 1
Drugs in phase 2 · 1
Trials reported · 3
- MATTERHORN · phase 3 · 2025 · positive
- CheckMate 649 · phase 3 · 2020 · positive
- KEYNOTE-859 · phase 3 · 2023 · positive
Ideas not yet in a trial · 1
Open problems and what is being done
Two assays with different thresholds leave patients near the cut-off in an uncertain position.
Most patients still progress within a year on chemo-immunotherapy.
How to combine PD-1 blockade with claudin 18.2 or HER2 therapy when targets overlap.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
Naples · cancer center | Italy | none recorded | 0 | 961 | 15,028 | - | |
New Haven, CT · cancer center | United States | 0 | 852 | 16,798 | - | ||
Madrid · hospital | Spain | none recorded | 0 | 764 | 13,767 | - | |
Taipei · hospital | Taiwan | none recorded | 0 | 746 | 8,966 | - | |
Lausanne · hospital | Switzerland | none recorded | 0 | 509 | 9,176 | - | |
Brussels · cancer center | Belgium | none recorded | 0 | 489 | 8,689 | - | |
Kyoto · hospital | Japan | none recorded | 0 | 251 | 1,942 | - | |
Navi Mumbai · research institute | India | none recorded | 0 | 175 | 1,127 | - | |
Philadelphia, PA · consortium | United States | none recorded | 0 | 165 | 1,237 | - | |
Lebanon, NH · cancer center | United States | 0 | 112 | 687 | - | ||
Neu-Isenburg · consortium | Germany | none recorded | 0 | 94 | 1,947 | none recorded | - |
Chicago, IL · consortium | United States | none recorded | 0 | 42 | 482 | - | |
Portland, OR · consortium | United States | none recorded | 0 | 42 | 1,880 | none recorded | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with PD-L1-high gastric cancer but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about PD-L1-high gastric cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example PD-L1 combined positive score, Epstein-Barr virus in situ hybridisation, Microsatellite instability and mismatch repair, HER2, Claudin 18.2), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include PD-L1 CPS 10 or above, PD-L1 CPS 5 or above, PD-L1 CPS 1 to 4.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Advanced, first line, CPS 5 or above
- For my situation (advanced, first line, cps 5 or above), which of the standard options do you recommend and why?Why: Guideline options include: Nivolumab with FOLFOX or CAPOX (CheckMate 649) or pembrolizumab with platinum-fluoropyrimidine chemotherapy (KEYNOTE-859).
- Am I a candidate for Nivolumab, Pembrolizumab, FOLFOX (5-FU, leucovorin, oxaliplatin) or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CheckMate 649 and KEYNOTE-859 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Advanced, first line, CPS 1 to 4
- For my situation (advanced, first line, cps 1 to 4), which of the standard options do you recommend and why?Why: Guideline options include: PD-1 antibody with chemotherapy is permitted in the United States and offered with a smaller expected gain; chemotherapy alone or zolbetuximab where claudin 18.2 is positive.
- Am I a candidate for Nivolumab, Pembrolizumab, Zolbetuximab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Resectable stage II to III
- For my situation (resectable stage ii to iii), which of the standard options do you recommend and why?Why: Guideline options include: Perioperative FLOT with durvalumab (MATTERHORN), given irrespective of PD-L1 score.
- Am I a candidate for Durvalumab, FLOT (5-FU, leucovorin, oxaliplatin, docetaxel), and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of MATTERHORN apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Second line
- For my situation (second line), which of the standard options do you recommend and why?Why: Guideline options include: Ramucirumab with paclitaxel (RAINBOW); no established role for continued PD-1 blockade.
- Am I a candidate for Ramucirumab, Paclitaxel / nab-paclitaxel, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of RAINBOW apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of MATTERHORN, Tislelizumab, Biomarker-directed first-line quadruplets in gastric cancer, Gotistobart?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Two assays with different thresholds leave patients near the cut-off in an uncertain position”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Most patients still progress within a year on chemo-immunotherapy”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with PD-L1-high gastric cancer, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
6targets
6drugs
12companies
8terms
1trials
4ideas
1Latest papers
topQuery for this cancer: (TITLE:"PD-L1-high gastric cancer" OR ABSTRACT:"PD-L1-high gastric cancer" OR TITLE:"PD-L1 CPS 5 or above gastric cancer" OR ABSTRACT:"PD-L1 CPS 5 or above gastric cancer" OR TITLE:"PD-L1-positive gastro-oesophageal adenocarcinoma" OR ABSTRACT:"PD-L1-positive gastro-oesophageal adenocarcinoma" OR TITLE:"EBV-positive gastric cancer PD-L1 high" OR ABSTRACT:"EBV-positive gastric cancer PD-L1 high") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about PD-L1-high gastric cancer, not a curated reading list.
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