PD-L1-high gastric cancer: the decisions you may face
4 treatment settings, 4 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, CPS 5 or above
Nivolumab with FOLFOX or CAPOX (CheckMate 649) or pembrolizumab with platinum-fluoropyrimidine chemotherapy (KEYNOTE-859).
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.
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.
FOLFOX is the workhorse chemotherapy combination for bowel cancer, used after surgery to cure and in advanced disease as the backbone that targeted drugs are added to.
CAPOX pairs the oral fluoropyrimidine capecitabine with intravenous oxaliplatin as a pill-based alternative to FOLFOX. For low-risk stage III colon cancer three months after surgery works as well as six and halves nerve damage; it is also standard in gastric cancer, with hand-foot syndrome as its price.
- First-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+ |
|---|---|---|
| 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+ |
|---|---|---|
| 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.
- Between Nivolumab, Pembrolizumab, FOLFOX (5-FU, leucovorin, oxaliplatin) 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 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 Nivolumab or 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, cps 5 or above), which of the standard options do you recommend and why?Why: Guideline options include: Nivolumab with FOLFOX or CAPOX (CheckMate 649) or pembrolizumab with platinum-fluoropyrimidine chemotherapy (KEYNOTE-859).
- Am I a candidate for Nivolumab, Pembrolizumab, FOLFOX (5-FU, leucovorin, oxaliplatin) 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 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, first line, CPS 1 to 4
PD-1 antibody with chemotherapy is permitted in the United States and offered with a smaller expected gain; chemotherapy alone or zolbetuximab where claudin 18.2 is positive.
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.
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.
Zolbetuximab is the first drug against Claudin 18.2, a protein exposed on stomach cancer cells. Added to chemotherapy it extends survival by two to three months; nausea is the price.
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+ |
|---|---|---|
| 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.
- Between Nivolumab, Pembrolizumab and Zolbetuximab, 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 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, cps 1 to 4), which of the standard options do you recommend and why?Why: Guideline options include: PD-1 antibody with chemotherapy is permitted in the United States and offered with a smaller expected gain; chemotherapy alone or zolbetuximab where claudin 18.2 is positive.
- Am I a candidate for Nivolumab, Pembrolizumab, Zolbetuximab, 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 stage II to III
Perioperative FLOT with durvalumab (MATTERHORN), given irrespective of PD-L1 score.
A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers.
FLOT is the four-drug chemotherapy given before and after surgery for stomach cancer in the West; since 2025 immunotherapy is added to it.
- Resectable stage II-IVA gastric/GEJ adenocarcinoma: perioperative FLOT + durvalumab vs FLOT + placebo
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.
- EFS HR 0.71; OS HR 0.78; 3-year OS 68.6%.
| 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 Durvalumab and FLOT (5-FU, leucovorin, oxaliplatin, docetaxel), 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 MATTERHORN, 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 Durvalumab 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 stage ii to iii), which of the standard options do you recommend and why?Why: Guideline options include: Perioperative FLOT with durvalumab (MATTERHORN), given irrespective of PD-L1 score.
- Am I a candidate for Durvalumab, 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.
- How do the results of MATTERHORN 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
Ramucirumab with paclitaxel (RAINBOW); no established role for continued PD-1 blockade.
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 advanced gastric/GEJ cancer: ramucirumab + paclitaxel vs paclitaxel
OS 9.6 vs 7.4 months, HR 0.81.
Overall survival (months): Ramucirumab + paclitaxel 9.6 (n=330) vs Placebo + paclitaxel 7.4 (n=335) · HR 0.81 · 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 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 RAINBOW, 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 (second line), which of the standard options do you recommend and why?Why: Guideline options include: Ramucirumab with paclitaxel (RAINBOW); no established role for continued PD-1 blockade.
- Am I a candidate for 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 RAINBOW 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.