Key points
- In stomach cancer that can be operated on, surgery alone is not enough: chemotherapy before and after surgery improves the chance of survival [1, 2].
- The four-drug FLOT regimen, every 2 weeks, 4 cycles before and 4 cycles after surgery, is today's standard treatment [2].
- Adding the immunotherapy drug durvalumab to FLOT lowered the chance of the cancer coming back and lengthened patients' lives [3, 4].
- In advanced cancer, four tumour tests (HER2, PD-L1, MSI and claudin 18.2) decide the right drug; ask your doctor for the results [5].
- Immunotherapy with chemotherapy, and the drug trastuzumab for HER2-positive tumours, have lengthened the lives of patients with advanced cancer [6, 8, 10].
- Nutrition is part of treatment; after the whole stomach is removed, lifelong vitamin B12 injections are recommended [20, 22].
The story of stomach cancer treatment
For years, the only treatment for stomach cancer that could be operated on was surgery, but in many patients the cancer came back: in a large study, fewer than 1 in every 4 patients who had surgery alone were alive 5 years later [1]. In 2006, the same study showed that chemotherapy before and after surgery shrinks the tumour before the operation and improves the chance of survival [1].
In 2019, the four-drug FLOT regimen (fluorouracil, leucovorin, oxaliplatin and docetaxel) did better than the previous regimen in a large study and lengthened patients' lives, without more serious side effects [2]. Six years later, adding the immunotherapy drug durvalumab to FLOT lowered the chance of the cancer coming back, and in about 1 in every 5 patients the tumour had completely disappeared by the time of surgery [3]; later it was shown to lengthen patients' lives as well [4].
In advanced HER2-negative cancer, with chemotherapy alone half of patients lived less than a year [6]. Since 2010 the targeted drug trastuzumab for HER2-positive tumours [10], since 2021 immunotherapy with chemotherapy (nivolumab and then pembrolizumab) [6, 8], and since 2023 the new drug zolbetuximab for claudin 18.2-positive tumours [12, 13] have lengthened patients' lives. In patients whose tumours had high PD-L1, with nivolumab plus chemotherapy about 1 in every 6 people was alive 5 years later; nearly three times as many as with chemotherapy alone [7].
Tumour tests: ask about these before treatment
HER2
A protein on the surface of the cancer cell. If there is a lot of it (HER2-positive), the targeted drug trastuzumab is added to chemotherapy and lengthens life [10, 5].
PD-L1 (CPS score)
MSI or dMMR
These tests are done with special stains on a sample of tumour tissue [29, 26]. The American Society of Clinical Oncology guideline recommends having the results as soon as possible, so that treatment can be chosen accordingly [5]. See: Biomarkers and targeted therapy and How to read your pathology report
Cancer that can be operated on: FLOT before and after surgery
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- 2
4 cycles of FLOT before surgery
One cycle every 2 weeks: three drugs are given on the same day, and fluorouracil runs slowly into a vein over 24 hours [2]. See: The FLOT regimen and Chemotherapy ports
- 3
- 4
- 5
Adding immunotherapy: durvalumab
Durvalumab is given every 4 weeks with FLOT before and after surgery, and then alone for 10 more doses; close to a year in total [27]. In a large study, this combination lowered the chance of the cancer coming back and lengthened patients' lives, without delaying surgery or increasing severe side effects [3, 4].
Advanced cancer: first treatment based on the tests
When stomach cancer has spread or cannot be operated on, the basis of treatment is two-drug chemotherapy: oxaliplatin with capecitabine or fluorouracil [5, 6]. The results of the tumour tests decide which drug is added to it [5]:
HER2-negative and PD-L1-positive
Chemotherapy with the immunotherapy drug nivolumab or pembrolizumab, usually when the PD-L1 score is 1 or more [5, 25, 26]. The higher the score, the greater the benefit [5, 9]. See: Nivolumab with CAPOX or FOLFOX
HER2-positive
Claudin 18.2-positive and HER2-negative
High MSI (dMMR)
None of these markers
Two-drug chemotherapy alone [5].
If the disease progresses
Weekly paclitaxel with ramucirumab [14, 5], or for HER2-positive tumours, trastuzumab deruxtecan [15, 5]. Single-drug chemotherapy (docetaxel or irinotecan) also lengthened life compared with supportive care alone [18].
Side effects: what to expect
With FLOT: in a large study, diarrhoea, nausea, numbness and tingling in the hands and feet, and tiredness affected about half of patients or more, and about 3 in every 10 people had hair loss [27]. A drop in white blood cells is also common and raises the risk of infection; take your temperature every day [27, 32, 35]. Numbness caused by oxaliplatin gets worse with cold; avoid cold drinks, ice and exposing your skin to the cold [34]. See: Numbness and tingling in the hands and feet and Low blood counts and preventing infection
Before fluorouracil or capecitabine: a test of the DPYD gene is recommended; a lack of an enzyme called DPD can cause very severe side effects [32, 33]. If you take warfarin (a blood thinner), be sure to tell your doctor [32, 33].
With immunotherapy (nivolumab, pembrolizumab, durvalumab): sometimes the immune system attacks healthy organs such as the lungs, bowel, liver, hormone glands, kidneys or skin; these side effects can occur even after treatment has ended [25, 26]. See: Side effects of immunotherapy
With zolbetuximab: nausea and vomiting are very common (7 to 8 in every 10 people had nausea), especially with the first doses; anti-sickness medicine is given before every infusion [29]. With trastuzumab deruxtecan: about 1 in every 7 patients developed lung inflammation, which was mostly mild; report a new cough or shortness of breath straight away [15]. See: Nausea and vomiting
Nutrition before, during and after stomach surgery
Stomach cancer and its treatment can make it hard to eat enough food or to absorb nutrients [24]. From diagnosis onwards, your weight and how much you eat should be checked regularly; if you are losing weight, nutritional advice, treatment of symptoms that make eating difficult and oral nutritional supplements help [20]. Enough protein (more than 1 gram per kilogram of body weight a day) is important [20].
- After stomach surgery: eat smaller meals more often; you may need to sit upright for a while after eating [24].
- Dumping syndrome: after stomach surgery, food sometimes passes into the bowel too quickly and you feel unwell after eating; sometimes blood sugar drops a few hours later. The first treatment is changing your diet [21].
- Vitamin B12: after the whole stomach is removed, vitamin B12 deficiency is very likely, and regular injections are recommended for life; after part of the stomach is removed, deficiency may also occur and need treatment [22]. See: Vitamin B12 deficiency
Read more: Nutrition during cancer treatment and What to eat before and after chemotherapy
When should I contact my doctor?
During chemotherapy: report straight away any fever or sign of infection, severe diarrhoea, painful mouth sores that stop you eating and drinking, or redness, blisters and pain on the palms or soles [32]. If during or after an oxaliplatin infusion you have chest tightness, shortness of breath, wheezing, dizziness or swelling of the face, eyelids or lips, get help straight away [34]. See: Fever and warning signs during chemotherapy. With immunotherapy: a new cough or shortness of breath, diarrhoea or severe abdominal pain, yellowing of the skin or eyes, severe nausea or vomiting, or a widespread rash [25, 26]. With trastuzumab: shortness of breath or a new cough, swelling of the ankles or face, palpitations or rapid weight gain [28]. If you have new chest pain, shortness of breath, severe dizziness or sudden confusion, call your local emergency number straight away [32].
Frequently asked questions
How many sessions of FLOT chemotherapy are there?
Usually 8 cycles, one every 2 weeks: 4 before and 4 after surgery [2]. If durvalumab is added, it continues alone for 10 more doses, every 4 weeks, after FLOT ends [27]. See: The FLOT regimen and How many chemotherapy sessions will I need?
Why is chemotherapy given before surgery? Wouldn't it be better to have the operation sooner?
Chemotherapy before surgery shrinks the tumour, and in large studies, together with chemotherapy after surgery, it lengthened patients' lives more than surgery alone [1, 2]. In one study, surgery was delayed in about 1 in every 10 patients in both groups, and adding immunotherapy did not increase this [3]. Make the decision with your treatment team.
Does immunotherapy help everyone with advanced stomach cancer?
What is zolbetuximab and who is it for?
An antibody that attaches to the claudin 18.2 protein on stomach cancer cells. It is for advanced HER2-negative, claudin-positive cancer, and in two large studies, given with chemotherapy, it lengthened patients' lives [12, 13]. The most common side effects are nausea and vomiting [29].
How should I eat after stomach surgery?
Can advanced stomach cancer be treated?
Usually the aim is long-term control of the disease, but newer treatments have lengthened patients' lives: with immunotherapy plus chemotherapy, in patients whose tumours had high PD-L1, about 1 in every 6 people was alive 5 years later [7]. See: Is stomach cancer curable?
For physicians
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Perioperative treatment: MAGIC (503 patients): 3 cycles of ECF before and 3 after surgery versus surgery alone, HR for death 0.75 and 5-year survival 36% vs 23% [1]. FLOT4 (716 patients, cT2 or higher and/or cN+, no distant metastases): FLOT (docetaxel 50, oxaliplatin 85, leucovorin 200 and fluorouracil 2600 mg/m² as a 24-hour infusion, all on day 1 every 2 weeks; 4 cycles before and 4 after surgery) versus ECF/ECX, median OS 50 vs 35 months (HR 0.77); related serious adverse events 27% in both groups and toxic deaths below 1% [2]. CLASSIC (1035 patients with stage II to IIIB after D2 gastrectomy): 8 cycles of adjuvant CAPOX, 3-year DFS 74% vs 59% (HR 0.56) [17]. MATTERHORN (948 patients, stage II to IVA): durvalumab 1500 mg every 4 weeks with FLOT, 2 cycles before and 2 after surgery, then 10 cycles of durvalumab alone; 2-year EFS 67.4% vs 58.5% (HR 0.71), pCR 19.2% vs 7.2%, grade 3–4 adverse events 71.6% vs 71.2% and delayed surgery 10.1% vs 10.8% [3]; in the overall survival analysis, HR 0.78 (95% CI 0.63 to 0.96; P=0.021) [4]. KEYNOTE-585 (804 patients in the main cohort): perioperative pembrolizumab, median OS 71.8 vs 55.7 months with HR 0.86 (95% CI 0.71 to 1.06) [19]. MSI: in an individual patient data meta-analysis of 4 trials (1556 patients; MSI-high 7.8%), 5-year OS 77.5% vs 59.3%, with no apparent benefit from chemotherapy in MSI-high tumours (DFS HR 1.27; 95% CI 0.53 to 3.04); the authors propose prospective study of omitting chemotherapy and/or immunotherapy in this group [16].
Advanced HER2-negative disease: CheckMate 649 (1581 patients): nivolumab 360 mg every 3 weeks with CAPOX or 240 mg every 2 weeks with FOLFOX [6]; with CPS 5 or more, median OS 14.4 vs 11.1 months (HR 0.71), and with CPS 1 or more, 14.0 vs 11.3 months (HR 0.77); with CPS below 1, HR 0.85 (95% CI 0.63 to 1.15), and in 44 patients with MSI-H, HR 0.37 [25]; at 5-year follow-up (CPS 5 or more), 5-year OS 16% vs 6% and objective response 58% vs 46%; treatment-related grade 3–4 adverse events 60% vs 45% [7]. KEYNOTE-859 (1579 patients): pembrolizumab 200 mg every 3 weeks for up to 35 cycles with FP or CAPOX [8]; at 4.5-year follow-up, median OS 12.9 vs 11.5 months in all patients (HR 0.78), 13.0 vs 11.4 months with CPS 1 or more (HR 0.74) and 15.8 vs 11.8 months with CPS 10 or more (HR 0.64); treatment-related grade 3–4 adverse events 58.3% vs 49.3% [9]. In an exploratory analysis with CPS below 1, HR 0.92 (95% CI 0.73 to 1.17) [26]; the FDA labels restrict both drugs to PD-L1 CPS 1 or more [25, 26]. SPOTLIGHT (565 patients with CLDN18.2-positive tumours, i.e. moderate-to-strong membranous staining in 75% or more of tumour cells): zolbetuximab + mFOLFOX6, median PFS 10.61 vs 8.67 months (HR 0.75) and HR for death 0.75; grade 3 or higher adverse events 87% vs 78% [12]. GLOW (507 patients): zolbetuximab + CAPOX, median PFS 8.21 vs 6.80 months (HR 0.687) and OS 14.39 vs 12.16 months (HR 0.771) [13]. Nausea 82% and vomiting 67% with mFOLFOX6; premedication with combination antiemetics (NK1 and/or 5-HT3 antagonists) before each infusion [29]. ASCO 2026: immunotherapy + doublet chemotherapy for pMMR/MSS HER2-negative disease with PD-L1 1 or more (benefit more likely with higher PD-L1); zolbetuximab for PD-L1 below 1 and CLDN18.2-positive; shared decision-making when both are positive; doublet chemotherapy alone without an actionable marker; immunotherapy alone or with chemotherapy for dMMR/MSI-H [5].
HER2-positive disease: ToGA (594 patients): trastuzumab + cisplatin with capecitabine or fluorouracil (6 cycles), median OS 13.8 vs 11.1 months (HR 0.74); cardiac adverse events 6% in both groups [10]. KEYNOTE-811 (698 patients): pembrolizumab 200 mg + trastuzumab + FP or CAPOX; at the second interim analysis median PFS 10.0 vs 8.1 months (HR 0.72) [11]; at the final analysis with CPS 1 or more (594 patients), median OS 20.1 vs 15.7 months (HR 0.79), PFS 10.9 vs 7.3 months and objective response 73% vs 58%; with CPS below 1, overall survival HR 1.10 (95% CI 0.72 to 1.68) [26]. ASCO: trastuzumab + doublet chemotherapy, adding pembrolizumab for PD-L1 1 or more [5].
Second line: RAINBOW (665 patients): ramucirumab 8 mg/kg on days 1 and 15 + paclitaxel 80 mg/m² on days 1, 8 and 15 every 28 days, median OS 9.6 vs 7.4 months (HR 0.807); grade 3 or higher neutropenia 41% vs 19% [14]. DESTINY-Gastric04 (494 patients with biopsy-confirmed HER2-positive disease after progression on trastuzumab): trastuzumab deruxtecan 6.4 mg/kg versus ramucirumab + paclitaxel, median OS 14.7 vs 11.4 months (HR 0.70), objective response 44.3% vs 29.1% and ILD or pneumonitis 13.9% [15]. Single-agent chemotherapy (docetaxel 60 mg/m² every 3 weeks or irinotecan 150 mg/m² every 2 weeks) versus supportive care: median OS 5.3 vs 3.8 months (HR 0.657) [18].
Safety points: test for DPYD variants before fluorouracil or capecitabine (unless treatment is urgent) and avoid them in variants causing complete DPD deficiency; bleeding risk with warfarin [32, 33]. Oxaliplatin: acute neuropathy triggered by cold; avoid cold drinks and ice [34]. Trastuzumab: assess LVEF before starting and periodically [28]. Docetaxel: monitor blood counts and fluid retention [35].
| Regimen | Dose and schedule | Note |
|---|---|---|
| Perioperative FLOT | Docetaxel 50, oxaliplatin 85, leucovorin 200 and fluorouracil 2600 mg/m² (24-hour infusion), all on day 1, every 2 weeks; 4 cycles before and 4 after surgery [2] | DPYD testing before starting [32] |
| Durvalumab + FLOT (MATTERHORN) | Durvalumab 1500 mg on day 1 with FLOT on days 1 and 15 of each 4-week cycle, 2 cycles before and 2 after surgery; then durvalumab 1500 mg every 4 weeks for up to 10 cycles; body weight below 30 kg: 20 mg/kg [27] | Durvalumab infused over 60 minutes [27] |
| Nivolumab + CAPOX or FOLFOX | Nivolumab 360 mg every 3 weeks with chemotherapy every 3 weeks, or 240 mg every 2 weeks with chemotherapy every 2 weeks [25] | FDA label: PD-L1 CPS 1 or more [25] |
| Pembrolizumab + FP or CAPOX | Pembrolizumab 200 mg every 3 weeks or 400 mg every 6 weeks [26]; in KEYNOTE-859: FP (fluorouracil 800 mg/m² per day on days 1 to 5 + cisplatin 80 mg/m² on day 1) or CAPOX (capecitabine 1000 mg/m² twice daily on days 1 to 14 + oxaliplatin 130 mg/m² on day 1), every 3 weeks [8] | FDA label: CPS 1 or more; up to 35 cycles in the trial [26, 8] |
| Zolbetuximab + mFOLFOX6 or CAPOX | First dose 800 mg/m², then 600 mg/m² every 3 weeks or 400 mg/m² every 2 weeks [29] | CLDN18.2-positive (75% or more of cells) and HER2-negative; antiemetics before each infusion; no dose reduction recommended [29] |
| Trastuzumab + chemotherapy (± pembrolizumab) | Trastuzumab 8 mg/kg as a 90-minute infusion, then 6 mg/kg every 3 weeks [28]; with CPS 1 or more, pembrolizumab 200 mg every 3 weeks for up to 24 months [26] | LVEF before starting and periodically [28] |
| Ramucirumab + paclitaxel (second line) | Ramucirumab 8 mg/kg on days 1 and 15 + paclitaxel 80 mg/m² on days 1, 8 and 15, every 28 days [14] | Premedicate with an IV histamine H1 antagonist before each ramucirumab infusion [30] |
| Trastuzumab deruxtecan (second line, HER2-positive) | 6.4 mg/kg IV every 3 weeks [31] | Dose reductions to 5.4 and then 4.4 mg/kg; monitor for ILD or pneumonitis [31, 15] |
Dose modifications for side effects, monitoring and further details are on each regimen's page.
Full doses, dose modifications and monitoring: FLOT · durvalumab + FLOT · nivolumab + CAPOX or FOLFOX · pembrolizumab + chemotherapy · zolbetuximab + chemotherapy · trastuzumab + chemotherapy · pembrolizumab + trastuzumab + chemotherapy · ramucirumab + paclitaxel · trastuzumab deruxtecan · CAPOX · FOLFOX. Biomarkers: lesson on molecular testing before treatment; lesson on DPYD testing; lesson on immunotherapy toxicity; lesson on cancer cachexia.
Scientific evidence
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Scientific evidence
14 itemsPerioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial
Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer
Perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable gastric and gastro-oesophageal junction adenocarcinoma (MATTERHORN): final results of overall survival and event-free survival by pathological response in a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial
Nivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 5-year follow-up results from CheckMate 649
Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial
Pembrolizumab plus chemotherapy as first-line therapy for advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma: 4.5-year follow-up from the randomized phase III KEYNOTE-859 study
Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial
Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial
Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial
Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial
Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial
Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer
Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline Update
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Related links
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Treatment guides
References
35 referencesShow all references, 15 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
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- 3
- 4Perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable gastric and gastro-oesophageal junction adenocarcinoma (MATTERHORN): final results of overall survival and event-free survival by pathological response in a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
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- 11Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial
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- 19Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of the Randomized, Phase III KEYNOTE-585 Study
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- 21International consensus on the diagnosis and management of dumping syndrome
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- 30CYRAMZA (ramucirumab) injection, for intravenous use: Prescribing Information
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This page is based on reputable scientific sources and was last updated on 29 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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