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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.
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.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
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.
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
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.
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Perioperative durvalumab with FLOT is a new standard for resectable gastric and junctional adenocarcinoma irrespective of PD-L1 expression.
Pembrolizumab plus chemotherapy is approved for HER2-negative advanced gastric cancer, alongside nivolumab plus chemotherapy from CheckMate 649, with strongest evidence at higher PD-L1 scores.
Patients with newly diagnosed advanced stomach or oesophageal adenocarcinoma whose tumour is HER2-negative and PD-L1 positive (CPS 5 or more, or at least 1 in some regions) should receive chemotherapy with nivolumab (or pembrolizumab, from KEYNOTE-859), which adds about three months of median survival and doubles the chance of being alive at three years. The benefit in PD-L1-negative tumours is doubtful, and these patients may be better served by chemotherapy alone or by trials.
FLOT is the reference perioperative regimen for gastric and junctional adenocarcinoma, and the backbone onto which durvalumab was added in MATTERHORN.
Ramucirumab-paclitaxel is the second-line standard for HER2-negative gastric cancer after chemo-immunotherapy, and the comparator for newer agents.
Query 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.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
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.
The bowel cancer regimens share low blood counts, tiredness, sickness and a sore mouth. Oxaliplatin adds cold-triggered tingling, irinotecan adds early and late diarrhoea, capecitabine adds hand-foot syndrome and needs a DPD test first, and cetuximab or panitumumab add an acne-like rash and low magnesium. The rule for all of them: ring the 24-hour number rather than wait.
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
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Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
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