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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
| Setting | Approach | Guideline |
|---|---|---|
| Localised | Perioperative FLOT ± durvalumab; D2 gastrectomy. | not mapped |
| Advanced first line | Chemotherapy + PD-1 ± trastuzumab ± zolbetuximab by biomarker. | not mapped |
| Later lines | T-DXd (HER2+), zanidatamab, CLDN18.2 CAR-T/ADC in trials. | ESMO-MCBS 2 (DESTINY-Gastric01 trastuzumab deruxtecan) |
| Prevention and screening | 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. | not mapped |
| Early (T1a) disease | Endoscopic submucosal dissection for well-differentiated mucosal tumours ≤2 cm without ulceration (expanded criteria in Japan); otherwise gastrectomy. | not mapped |
| Resectable stage II-III (Western) | Perioperative FLOT + durvalumab (MATTERHORN: OS HR 0.78, pCR 19%) with D2 gastrectomy; FOLFOX/CAPOX perioperatively for patients unfit for docetaxel. | NCCN Category 1 (perioperative FLOT) |
| Resectable stage II-III (Asian practice) | D2 gastrectomy then adjuvant S-1 (ACTS-GC) or CAPOX (CLASSIC) for 6-12 months; neoadjuvant approaches increasingly adopted. | not mapped |
| Advanced, HER2-positive, first line | 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). | NCCN Category 1 (trastuzumab + chemo ± pembrolizumab) |