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A cancer with three new targets in five years: Claudin 18.2, FGFR2b, and HER2 with new ADCs, plus immunotherapy in first line.
Gastric and gastro-oesophageal junction adenocarcinoma is curable when found early: Japan and Korea screen endoscopically and cure most cases. It causes about one million new cases a year, concentrated in East Asia, Eastern Europe, and Latin America, where Helicobacter pylori infection, salt, and smoking drive incidence; elsewhere two-thirds present with advanced disease, which is why it accounts for 660,000 deaths a year and five-year survival outside screened populations is under 30%. Biology splits by the Lauren classification (intestinal vs diffuse) and the TCGA classes (EBV-positive, MSI, genomically stable, chromosomally unstable), and clinically by three actionable biomarkers: HER2 (~15-20%), PD-L1 (CPS ≥5 in ~60%), and Claudin 18.2 (~38% at the approval threshold), with FGFR2b, MSI, and EBV as further strata.
Localised disease is treated with gastrectomy and D2 lymphadenectomy plus perioperative chemotherapy: FLOT in the West, adjuvant S-1 or CAPOX in Asia. MATTERHORN (2025) added durvalumab to FLOT, the first perioperative immunotherapy with an overall survival benefit (3-year OS 68.6%). Advanced disease is stratified at diagnosis: HER2-positive tumours get trastuzumab + chemotherapy + pembrolizumab (KEYNOTE-811) or, after HERIZON-GEA-01, zanidatamab + chemotherapy ± tislelizumab; HER2-negative, PD-L1 CPS ≥5 tumours get nivolumab or pembrolizumab with chemotherapy (CheckMate 649 5-year OS 16% vs 6%); CLDN18.2-positive tumours get zolbetuximab + chemotherapy (SPOTLIGHT/GLOW). Second line: T-DXd for HER2-positive disease (DESTINY-Gastric04, OS 14.7 vs 11.4 months), ramucirumab + paclitaxel otherwise, and from 2026 the CLDN18.2 ADC sonesitatug vedotin (CLARITY-Gastric 01). Third line: trifluridine/tipiracil.
The frontier is Claudin 18.2 (ADCs, CAR-T satri-cel approved in China, bispecifics), biomarker overlap and combination quadruplets, peritoneal-directed therapy for the commonest site of relapse, FGFR2b after the mixed FORTITUDE-101 result, and ctDNA-guided perioperative strategies. Diffuse-type and genomically stable tumours remain the least treatable subgroup.
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.
~1 million cases per year, the fifth most common cancer; where endoscopic screening finds it early (Korea, Japan) most cases are cured.
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: HER2-positive gastric cancer, Claudin 18.2-positive gastric cancer, PD-L1-high 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
Most people reading this do not have advanced disease. The map describes what can happen over the whole course of the illness, across autopsy and registry series; today's staging scans find spread earlier, and each site has treatments, from focused radiotherapy for a few spots to drugs that reach the brain.
What helpsChemotherapy plus nivolumab or pembrolizumab, trastuzumab or zanidatamab for HER2, zolbetuximab for Claudin 18.2, T-DXd second line; peritoneal-directed therapy is an active front.
Background: Peritoneal metastasis. Also on OnCo: Atlas of advanced disease · How cancer spreads: the metastasis stages.
Diffuse-type tumours seed the peritoneum; staging laparoscopy looks for it.
Intestinal-type tumours favour the liver.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Perioperative FLOT ± durvalumab; D2 gastrectomy.
Chemotherapy + PD-1 ± trastuzumab ± zolbetuximab by biomarker.
T-DXd (HER2+), zanidatamab, CLDN18.2 CAR-T/ADC in trials.
H. pylori eradication reduces incidence; endoscopic screening programmes in Japan and Korea (biennial from age 40-50) detect most cancers at a curable stage. No population screening in the West. Prophylactic total gastrectomy for germline CDH1 carriers.
Endoscopic submucosal dissection for well-differentiated mucosal tumours ≤2 cm without ulceration (expanded criteria in Japan); otherwise gastrectomy.
Perioperative FLOT + durvalumab (MATTERHORN: OS HR 0.78, pCR 19%) with D2 gastrectomy; FOLFOX/CAPOX perioperatively for patients unfit for docetaxel.
D2 gastrectomy then adjuvant S-1 (ACTS-GC) or CAPOX (CLASSIC) for 6-12 months; neoadjuvant approaches increasingly adopted.
Trastuzumab + fluoropyrimidine/platinum + pembrolizumab (KEYNOTE-811, PD-L1 CPS ≥1); zanidatamab + chemotherapy ± tislelizumab after HERIZON-GEA-01 (PFS 12.4 vs 8.1 months; sBLA 2026).
Nivolumab (CheckMate 649) or pembrolizumab (KEYNOTE-859) or tislelizumab (RATIONALE-305) with FOLFOX or CAPOX; add zolbetuximab if CLDN18.2-positive (sequencing/combination under study).
Zolbetuximab + mFOLFOX6 or CAPOX (SPOTLIGHT/GLOW). PD-L1 CPS ≥5 double-positives: either add-on; combination trials ongoing.
FOLFOX or CAPOX chemotherapy alone; MSI-high tumours get PD-1 blockade regardless of CPS.
Trastuzumab deruxtecan 6.4 mg/kg (DESTINY-Gastric04, OS 14.7 vs 11.4 months) if HER2 persists on re-biopsy or ctDNA.
Ramucirumab + paclitaxel (RAINBOW, OS 9.6 vs 7.4 months); CLDN18.2-positive: sonesitatug vedotin after CLARITY-Gastric 01 (2026) or satri-cel CAR-T (China).
Trifluridine/tipiracil (TAGS, OS 5.7 vs 3.6 months); irinotecan; clinical trials (FGFR2b, CLDN18.2 bispecifics, T-cell engagers).
Systemic therapy; intraperitoneal paclitaxel, HIPEC, and PIPAC in trials; palliative gastrectomy not recommended (REGATTA).
Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year.
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.
The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask.
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.
Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked.