Microsatellite-unstable (MSI-high) gastric cancer: the decisions you may face
4 treatment settings, 2 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
PD-1 antibody with or without chemotherapy (nivolumab or pembrolizumab); nivolumab with ipilimumab in selected patients; the benefit exceeds that in any other subgroup.
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.
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer.
- Tests NivolumabFirst-line HER2-negative advanced gastric/GEJ/oesophageal adenocarcinoma: nivolumab + chemotherapy vs chemotherapy
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.
- CPS ≥5: OS 14.4 vs 11.1 months (HR 0.71); 5-year OS 16% vs 6%.
Overall survival, PD-L1 CPS ≥5 (months): Nivolumab + chemotherapy 14.4 (n=473) vs Chemotherapy 11.1 (n=482) · HR 0.71 · source - Tests PembrolizumabFirst-line HER2-negative advanced gastric/GEJ adenocarcinoma: pembrolizumab + chemotherapy vs placebo + chemotherapy
OS HR 0.78 (all); CPS ≥10 OS 15.7 vs 11.8 months (HR 0.65).
Overall survival, all randomised (months): Pembrolizumab + chemotherapy 12.9 (n=790) vs Placebo + chemotherapy 11.5 (n=789) · HR 0.78 · 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.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis (with nivolumab 1+3) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 25% | 14.4% |
| Hepatitis (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 15% | 13.4% |
| Rash (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 28% | 4.8% |
| Adrenal insufficiency (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 8% | 2.6% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Pembrolizumab, Nivolumab and Ipilimumab, 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 CheckMate 649 and KEYNOTE-859, 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 or Nivolumab 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: PD-1 antibody with or without chemotherapy (nivolumab or pembrolizumab); nivolumab with ipilimumab in selected patients; the benefit exceeds that in any other subgroup.
- Am I a candidate for Pembrolizumab, Nivolumab, Ipilimumab, 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 CheckMate 649 and KEYNOTE-859 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.
Advanced, after chemotherapy
Pembrolizumab under its tumour-agnostic approval for mismatch repair-deficient cancers.
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.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
| 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.
- Is Pembrolizumab 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.
- 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, after chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Pembrolizumab under its tumour-agnostic approval for mismatch repair-deficient cancers.
- Am I a candidate for Pembrolizumab, 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.
Resectable
Surgery with or without perioperative chemotherapy, whose benefit is doubtful here; neoadjuvant immunotherapy (nivolumab-ipilimumab, durvalumab-tremelimumab) in trials or where available.
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer.
A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers.
Tremelimumab is AstraZeneca's CTLA-4 antibody, given as a single priming dose with durvalumab and chemotherapy in lung and liver cancer.
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.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis (with nivolumab 1+3) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 25% | 14.4% |
| Hepatitis (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 15% | 13.4% |
| Rash (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 28% | 4.8% |
| Adrenal insufficiency (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 8% | 2.6% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Pneumonitis (any cause, PACIFIC) · vs 12.8% placebo; 1.1% fatal | 18.3% | - |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Nivolumab, Ipilimumab, Durvalumab 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.
- Which side effects of Nivolumab or Ipilimumab 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 (resectable), which of the standard options do you recommend and why?Why: Guideline options include: Surgery with or without perioperative chemotherapy, whose benefit is doubtful here; neoadjuvant immunotherapy (nivolumab-ipilimumab, durvalumab-tremelimumab) in trials or where available.
- Am I a candidate for Nivolumab, Ipilimumab, Durvalumab or related drugs, 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.
Hereditary risk
Germline testing and Lynch syndrome surveillance where the pattern suggests it.
A test of the DNA you were born with, to find inherited risk genes such as BRCA or Lynch syndrome.
- Actionable for patient and relatives
- Cheap
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- VUS burden
- Uptake and counselling capacity
- Is Germline (hereditary) testing 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 (hereditary risk), which of the standard options do you recommend and why?Why: Guideline options include: Germline testing and Lynch syndrome surveillance where the pattern suggests it.
Add these to your appointment list, or take the full question set for this cancer.