HER2-positive gastric cancer: the decisions you may face
4 treatment settings, 3 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
Advanced, first line
Trastuzumab with a platinum and a fluoropyrimidine (ToGA), plus pembrolizumab when PD-L1 CPS is 1 or above (KEYNOTE-811).
The first targeted antibody for a solid tumour (1998), which turned HER2-positive breast cancer from the worst subtype into one of the most treatable.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
Cisplatin is the original platinum chemotherapy, discovered by accident in 1965; it cures testicular cancer and makes radiation work better in cervical and head and neck cancer.
The platinum drug that works in bowel cancer where cisplatin does not, the 'OX' in FOLFOX and CAPOX; its cost is nerve damage in hands and feet.
Capecitabine (Xeloda) is a tablet form of the chemotherapy fluorouracil. It is a backbone of treatment for bowel cancer and a standard option in advanced breast cancer.
The 1957 chemotherapy that remains the backbone of treatment for bowel, stomach, pancreatic, anal, head and neck and breast cancers, and as a cream for skin precancers.
- Tests TrastuzumabFirst-line HER2-positive advanced gastric/GEJ adenocarcinoma: trastuzumab + cisplatin/fluoropyrimidine vs chemotherapy
OS 13.8 vs 11.1 months, HR 0.74.
Overall survival (months): Trastuzumab + chemotherapy 13.8 (n=294) vs Chemotherapy 11.1 (n=290) · HR 0.74 · source
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
- Cold-triggered acute neuropathy: avoid cold drinks and air for days after infusion.
- Possible QT prolongation. QT prolongation and torsades reported post-marketing; correct electrolytes.
- Reduce to 65 mg/m² for CrCl below 30.
- Capecitabine: take within 30 minutes after a meal. DPD deficiency (DPYD variants) causes severe toxicity: pre-treatment genotyping is recommended in Europe.
- Capecitabine: reduce to 75% for CrCl 30-50; contraindicated below 30.
- Between Trastuzumab, Pembrolizumab, Cisplatin and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in ToGA, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Pembrolizumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- 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.
Add these to your appointment list, or take the full question set for this cancer.
Second line
Trastuzumab deruxtecan (DESTINY-Gastric01 and DESTINY-Gastric04); ramucirumab with paclitaxel where the conjugate is unavailable.
Trastuzumab deruxtecan (Enhertu) is the most successful ADC ever. It redefined HER2 by working in tumours with only tiny amounts of the protein, and in 2026 moved into early-stage breast cancer.
An antibody that blocks the VEGF receptor, approved in liver cancer only for patients with a high AFP blood level, the first biomarker-selected HCC drug.
A microtubule poison discovered in the Pacific yew tree, among the most used chemotherapies in breast, lung, and ovarian cancer.
- Second-line HER2-positive gastric/GEJ cancer after trastuzumab: T-DXd vs ramucirumab + paclitaxel
OS 14.7 vs 11.4 months, HR 0.70.
Overall survival (months): T-DXd 6.4 mg/kg 14.7 (n=246) vs Ramucirumab + paclitaxel 11.4 (n=248) · HR 0.7 · source
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Neutropenia · DESTINY-Breast03/04; all-grade rates ≥20% per label | - | 18% |
| Nausea · DESTINY-Breast03/04; all-grade rates ≥20% per label | - | 7% |
| Anaemia · DESTINY-Breast03/04; all-grade rates ≥20% per label | - | 7% |
| Fatigue · DESTINY-Breast03/04; all-grade rates ≥20% per label | - | 6% |
- Interstitial lung disease in 10-15%: hold for any respiratory symptom and image; permanently discontinue for grade 2 or above. Moderately emetogenic: three-drug prophylaxis.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Trastuzumab deruxtecan, Ramucirumab and Paclitaxel / nab-paclitaxel, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in DESTINY-Gastric04, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Trastuzumab deruxtecan are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- 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.
Add these to your appointment list, or take the full question set for this cancer.
Later lines
Trifluridine-tipiracil; trials of zanidatamab and other HER2 agents.
An oral chemotherapy pill for bowel cancer that has stopped responding to everything else; with bevacizumab it extends life by about three months.
Zanidatamab (Ziihera) is an antibody that grabs HER2 at two different spots, approved for HER2+ bile duct cancer.
- Tests ZanidatamabFirst-line HER2-positive advanced gastro-oesophageal adenocarcinoma: zanidatamab + chemotherapy ± tislelizumab vs trastuzumab + chemotherapy
PFS 12.4 vs 8.1 months (HR 0.63-0.65); OS significantly improved.
Progression-free survival (months): Zanidatamab + chemotherapy + tislelizumab 12.4 vs Zanidatamab + chemotherapy 12.4 vs Trastuzumab + chemotherapy 8.1 · source
No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.
- Between Trifluridine/tipiracil and Zanidatamab, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in HERIZON-GEA-01, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- 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.
Add these to your appointment list, or take the full question set for this cancer.
Localised disease
Perioperative FLOT and gastrectomy as for HER2-negative disease; adding HER2 therapy before surgery is unproven.
FLOT is the four-drug chemotherapy given before and after surgery for stomach cancer in the West; since 2025 immunotherapy is added to it.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.
- Is FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?Why: A single standard does not mean a single choice; timing and trials are decisions too.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- 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.
Add these to your appointment list, or take the full question set for this cancer.