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HER2-positive gastric cancer overexpresses the HER2 growth receptor and is treated with trastuzumab added to chemotherapy, now usually with pembrolizumab as well. After progression the antibody-drug conjugate trastuzumab deruxtecan gives responses that plain chemotherapy cannot.
HER2 positivity is defined in stomach cancer as immunohistochemistry 3+ or 2+ with amplification on in situ hybridisation, and every advanced gastric or junctional adenocarcinoma is tested at diagnosis. HER2-positive tumours are more often intestinal type and sit more often at the junction than in the distal stomach; staining is heterogeneous, so biopsies from several sites are recommended and a negative result on a small sample can be wrong.
ToGA (Lancet 2010) added trastuzumab to cisplatin and a fluoropyrimidine and extended median overall survival from 11.1 to 13.8 months, and to 16.0 months in patients with strong HER2 expression; it made trastuzumab the first targeted therapy in stomach cancer. KEYNOTE-811 then added pembrolizumab to trastuzumab and chemotherapy, raising response rates and improving survival in PD-L1-positive tumours, so the triplet is now first-line standard where PD-L1 is expressed. Zanidatamab, a bispecific HER2 antibody, is being tested against trastuzumab in the same setting in HERIZON-GEA-01.
DESTINY-Gastric01 (NEJM 2020) showed that trastuzumab deruxtecan, an antibody-drug conjugate carrying a topoisomerase inhibitor payload, produced responses in 51 percent of previously treated patients against 14 percent with chemotherapy and improved median survival from 8.4 to 12.5 months, earning FDA approval in 2021. DESTINY-Gastric04 confirmed the benefit in the second line against ramucirumab and paclitaxel, with median survival of 14.7 against 11.4 months. Interstitial lung disease is the toxicity that needs watching. HER2 expression is often lost after trastuzumab, so a fresh biopsy before second-line HER2 therapy is advised.
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.
About one in six advanced gastric and junctional adenocarcinomas, commoner in intestinal-type and junctional tumours than in diffuse-type disease; it was the first molecular subgroup of stomach cancer to get its own treatment.
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, 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
Trastuzumab with a platinum and a fluoropyrimidine (ToGA), plus pembrolizumab when PD-L1 CPS is 1 or above (KEYNOTE-811).
Trastuzumab deruxtecan (DESTINY-Gastric01 and DESTINY-Gastric04); ramucirumab with paclitaxel where the conjugate is unavailable.
Trifluridine-tipiracil; trials of zanidatamab and other HER2 agents.
Perioperative FLOT and gastrectomy as for HER2-negative disease; adding HER2 therapy before surgery is unproven.
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Pembrolizumab with trastuzumab and chemotherapy is the first-line standard for HER2-positive gastric cancer with a PD-L1 combined positive score of 1 or more.
Trastuzumab deruxtecan is the standard second- or third-line treatment for HER2-positive gastric cancer, later confirmed against ramucirumab-paclitaxel in DESTINY-Gastric04.
FLOT is the reference perioperative regimen for gastric and junctional adenocarcinoma, and the backbone onto which durvalumab was added in MATTERHORN.
ToGA made gastric cancer the second disease treated by HER2 status and introduced gastric-specific HER2 scoring. It is the base on which trastuzumab deruxtecan and pembrolizumab combinations in HER2-positive gastric cancer have built.
Query for this cancer: (TITLE:"HER2-positive gastric cancer" OR ABSTRACT:"HER2-positive gastric cancer" OR TITLE:"HER2-positive gastro-oesophageal adenocarcinoma" OR ABSTRACT:"HER2-positive gastro-oesophageal adenocarcinoma" OR TITLE:"ERBB2-amplified gastric cancer" OR ABSTRACT:"ERBB2-amplified gastric cancer" OR TITLE:"HER2+ GEA" OR ABSTRACT:"HER2+ GEA") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about HER2-positive 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.
Sudden severe abdominal pain, a hard or very tender abdomen, or abdominal pain with vomiting and fever. Boxed warning for gastrointestinal perforation on bevacizumab.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Any new or worsening cough, breathlessness or fever. The label says to interrupt treatment for any suspected ILD and to permanently discontinue for grade 2 or higher.
Temperature of 38 C or higher, or feeling shivery and unwell even without a fever. Antibody-drug conjugates suppress the bone marrow, and several carry a boxed warning for severe neutropenia.
Capecitabine: take within 30 minutes after a meal. DPD deficiency (DPYD variants) causes severe toxicity: pre-treatment genotyping is recommended in Europe.
See all on the product pages:CapecitabineCisplatinFLOT (5-FU, leucovorin, oxaliplatin, docetaxel)Fluorouracil (5-FU)OxaliplatinPaclitaxel / nab-paclitaxelPembrolizumabRamucirumabTrastuzumab deruxtecanTrifluridine/tipiracil·Printable cards in the navigator
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