HER2-positive gastric cancer

aka HER2-positive gastro-oesophageal adenocarcinoma, ERBB2-amplified gastric cancer, HER2+ GEA

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.

Part ofGastric & gastro-oesophageal junction cancer

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.

State of the art

ToGA made HER2 the first biomarker in stomach cancer and trastuzumab-chemotherapy the standard first line for fifteen years.
Pembrolizumab added to trastuzumab and chemotherapy is now the first-line triplet in PD-L1-positive tumours.

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.

Trastuzumab deruxtecan gives a second HER2-directed line with a real survival gain, unlike lapatinib and trastuzumab emtansine before it.

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Bleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Capecitabine Cisplatin FLOT (5-FU, leucovorin, oxaliplatin, docetaxel)Fluorouracil (5-FU)Oxaliplatin Paclitaxel / nab-paclitaxel Trifluridine/tipiracil source
Emergency services now
Blood clot (lenalidomide, pomalidomide, thalidomide)
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
Capecitabine Fluorouracil (5-FU)source
Emergency services now
Bowel 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.
Ramucirumab source
Emergency services now
Hypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Pembrolizumab source
Emergency services now
Skin reaction
Blisters, peeling, or sores in the mouth or eyes with a rash. Enfortumab vedotin carries a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis, mostly in the first cycle.
Trastuzumab deruxtecan source
Call the 24-hour line now
Interstitial lung disease or pneumonitis
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.
Trastuzumab deruxtecan source

See all on the product pages:Capecitabine Cisplatin FLOT (5-FU, leucovorin, oxaliplatin, docetaxel)Fluorouracil (5-FU)Oxaliplatin Paclitaxel / nab-paclitaxel Pembrolizumab Ramucirumab Trastuzumab deruxtecan Trifluridine/tipiracil·Printable cards in the navigator

Anatomy and lymph node drainage

Oesophagus and stomach: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

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.

Subsites

Upper and middle oesophagus (squamous)
Lower oesophagus and junction (adenocarcinoma)HER2-positive junctional adenocarcinoma
Cardia and fundus
Body (diffuse or intestinal type)HER2 3+ by immunohistochemistry · HER2 2+ with amplification on in situ hybridisation · HER2-positive, PD-L1 CPS 1 or above (trastuzumab, pembrolizumab and chemotherapy) · HER2-positive junctional adenocarcinoma · HER2 loss after trastuzumab
Antrum and pylorus
Muscle wall (GIST)

Regional lymph nodes

perigastric (greater and lesser curve)
coeliac and hepatic
mediastinal
cervical (upper oesophagus)

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

Who gets it and what has changed

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.

Group

gastrointestinal

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Lines of therapy by subgroup →Staging and risk scores →

Decisions you may face

3 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

Advanced, first line6 Second line3 Later lines2 Localised disease

Advanced, first line

Trastuzumab with a platinum and a fluoropyrimidine (ToGA), plus pembrolizumab when PD-L1 CPS is 1 or above (KEYNOTE-811).

ToGATrastuzumabPembrolizumabCisplatinOxaliplatinCapecitabineFluorouracil (5-FU)HER2 HER2 sequence in gastric cancer: zanidatamab/trastuzumab + chemo ± PD-1 → T-DXd

Second line

Trastuzumab deruxtecan (DESTINY-Gastric01 and DESTINY-Gastric04); ramucirumab with paclitaxel where the conjugate is unavailable.

Trastuzumab deruxtecanDESTINY-Gastric04RamucirumabPaclitaxel / nab-paclitaxel

Later lines

Trifluridine-tipiracil; trials of zanidatamab and other HER2 agents.

Trifluridine/tipiracilZanidatamabHERIZON-GEA-01

Localised disease

Perioperative FLOT and gastrectomy as for HER2-negative disease; adding HER2 therapy before surgery is unproven.

FLOT (5-FU, leucovorin, oxaliplatin, docetaxel)Gastrectomy

Subtypes & biomarkers

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Subtypes

HER2 3+ by immunohistochemistry
HER2 2+ with amplification on in situ hybridisation
HER2-positive, PD-L1 CPS 1 or above (trastuzumab, pembrolizumab and chemotherapy)
HER2-positive junctional adenocarcinoma
HER2 loss after trastuzumab

Biomarkers clinicians test

HER2 by immunohistochemistry and in situ hybridisation (multiple biopsy sites)
PD-L1 combined positive score (decides pembrolizumab in first line)
HER2 status on repeat biopsy at progression
ERBB2 amplification on plasma ctDNA (trials)

How often this target appears

History

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2010ToGA: trastuzumab plus chemotherapy extends survival in HER2-positive gastric cancer
ToGATrastuzumab
2017GATSBY: trastuzumab emtansine fails in the second line
2020DESTINY-Gastric01: trastuzumab deruxtecan beats chemotherapy after trastuzumab
Trastuzumab deruxtecan
2021FDA approves trastuzumab deruxtecan for HER2-positive gastric cancer; KEYNOTE-811 adds pembrolizumab first line
Trastuzumab deruxtecanPembrolizumab
2025DESTINY-Gastric04: trastuzumab deruxtecan beats ramucirumab-paclitaxel in the second line
DESTINY-Gastric04

What changed

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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 →

FollowWatch this cancer and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for HER2-positive gastric cancer, drawn from the whole corpus: 4 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.

Trials reported · 3

HERIZON-GEA-01 · phase 3 · 2026 · positive
DESTINY-Gastric04 · phase 3 · 2025 · positive
ToGA · phase 3 · 2010 · positive

Combinations being explored · 1

HER2 sequence in gastric cancer: zanidatamab/trastuzumab + chemo ± PD-1 → T-DXd

Open problems and what is being done

HER2 heterogeneity and loss after treatment make a single biopsy unreliable.
No HER2-directed therapy has yet improved cure rates in resectable disease.
Interstitial lung disease with trastuzumab deruxtecan needs early recognition.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

HER2-positive gastric cancer

condition: HER2-positive gastric cancer

Open on ClinicalTrials.gov →

within

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

DESTINY-Gastric04 HERIZON-GEA-01 ToGA

Expert centres

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Where the expertise is

Expert centres

28 centres in 13 countries · 0 with a trial for this cancer on record · second-opinion finder →

Choose a region from the globe in the header to mark centres near you.

28 centres


Gustave Roussy Villejuif · cancer center	France	none recorded	1,855	31,182	ZAP-X gyroscopic radiosurgery Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)	#6
Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center Baltimore · cancer center	United States	NCI comprehensive	2,955	41,449	Multi-cancer early detection (MCED)Liquid biopsy (ctDNA)Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems +2	#10
National Cancer Center Hospital Tokyo · government	Japan	none recorded	1,599	21,937	none recorded	#13
Cancer Hospital, Chinese Academy of Medical Sciences Beijing · cancer center	China	none recorded	371	4,070	none recorded	#50
UCLA Jonsson Comprehensive Cancer Center Los Angeles · cancer center	United States	NCI comprehensive	2,019	32,934	PSMA PET MR-guided adaptive radiotherapy	-
Peking University Cancer Hospital Beijing · cancer center Programme: Gastric and oesophageal cancer	China	none recorded	1,344	18,195	CAR-T cell therapy Immune checkpoint inhibitors Antibody-drug conjugate (ADC)	-
Istituto Oncologico Veneto IRCCS Padua · cancer center	Italy	none recorded	962	12,326	Monoclonal antibodies Immune checkpoint inhibitors CDK4/6 inhibitors	-
Lausanne University Hospital (CHUV) / Ludwig Institute Lausanne Lausanne · hospital	Switzerland	none recorded	509	9,176	TIL therapy TCR-T cell therapy Immune checkpoint inhibitors Personalised neoantigen (mRNA) vaccines	-
Institut Jules Bordet Brussels · cancer center	Belgium	none recorded	489	8,689	Liquid biopsy (ctDNA)Monoclonal antibodies RNA sequencing & expression profiling Endocrine therapy (SERMs, AIs, SERDs)	-
Hospital del Mar / Hospital del Mar Research Institute Barcelona · hospital	Spain	none recorded	431	4,125	CAR-T cell therapy T-cell engagers (bispecific)Monoclonal antibodies	-
IRCCS Ospedale San Raffaele Milan · hospital	Italy	none recorded	399	5,644	TCR-T cell therapy CAR-T cell therapy Allogeneic (off-the-shelf) cell therapy Robotic & minimally invasive surgery	-
Istituto di Candiolo IRCCS (FPO) Candiolo · cancer center	Italy	none recorded	324	4,466	Patient-derived xenografts Liquid biopsy (ctDNA)Small-molecule kinase inhibitors Monoclonal antibodies	-
Weizmann Institute of Science Rehovot · research institute	Israel	none recorded	183	3,727	Monoclonal antibodies Single-cell & spatial profiling CRISPR functional genomics Proteomics & phosphoproteomics	-
GOG Foundation Philadelphia, PA · consortium	United States	none recorded	165	1,237	Immune checkpoint inhibitors Antibody-drug conjugate (ADC)Anti-angiogenic therapy	-
Indiana University Melvin and Bren Simon Comprehensive Cancer Center Indianapolis, IN · cancer center	United States	NCI comprehensive	159	4,238	Platinum agents Cytotoxic chemotherapy Allogeneic stem cell transplantation	-

(showing the first 15)

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 HER2-positive 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.

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost. The second-opinion finder explains how referral works in your country.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about HER2-positive gastric cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 20 questions

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 HER2 by immunohistochemistry and in situ hybridisation, PD-L1 combined positive score, HER2 status on repeat biopsy at progression, ERBB2 amplification on plasma ctDNA), 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 HER2 3+ by immunohistochemistry, HER2 2+ with amplification on in situ hybridisation, HER2-positive, PD-L1 CPS 1 or above.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

Advanced, first line

For my situation (advanced, first line), which of the standard options do you recommend and why?
Why: Guideline options include: Trastuzumab with a platinum and a fluoropyrimidine (ToGA), plus pembrolizumab when PD-L1 CPS is 1 or above (KEYNOTE-811).
Am I a candidate for Trastuzumab, Pembrolizumab, Cisplatin 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 ToGA 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: Trastuzumab deruxtecan (DESTINY-Gastric01 and DESTINY-Gastric04); ramucirumab with paclitaxel where the conjugate is unavailable.
Am I a candidate for Trastuzumab deruxtecan, 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 DESTINY-Gastric04 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Later lines

For my situation (later lines), which of the standard options do you recommend and why?
Why: Guideline options include: Trifluridine-tipiracil; trials of zanidatamab and other HER2 agents.
Am I a candidate for Trifluridine/tipiracil, Zanidatamab, 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 HERIZON-GEA-01 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Localised disease

For my situation (localised disease), which of the standard options do you recommend and why?
Why: Guideline options include: Perioperative FLOT and gastrectomy as for HER2-negative disease; adding HER2 therapy before surgery is unproven.
Am I a candidate for 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.

Any stage

Are there clinical trials I could join, for example of Zanidatamab, HERIZON-GEA-01, Disitamab vedotin, HER2 sequence in gastric cancer: zanidatamab/trastuzumab + chemo ± PD-1 → T-DXd?
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 “HER2 heterogeneity and loss after treatment make a single biopsy unreliable”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “No HER2-directed therapy has yet improved cure rates in resectable disease”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.