The first 60 days: HER2-positive gastric cancer
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. Below, week by week, is what OnCo's record of HER2-positive gastric cancer says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- SurgeonNamed in the standard of care for: Localised disease.
- Medical oncologistNamed in the standard of care for: Advanced, first line, Second line, Later lines, Localised disease.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Perioperative FLOT and gastrectomy as for HER2-negative disease; adding HER2 therapy before surgery is unproven.
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.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?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?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?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?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?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?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ToGA apply to someone like me?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?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?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of DESTINY-Gastric04 apply to someone like me?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?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?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?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?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?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?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?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?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?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?Open problems are where trials and second opinions matter most.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- HER2-positive gastric cancer: the full pageHER2-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.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Gastrectomy: Removing part (subtotal) or all (total) of the stomach for stomach cancer, with the bowel joined to what remains.
Every term links to the glossary.