The news at a glance
- This study included about a thousand patients with stomach cancer that could be removed with surgery: half had the usual chemotherapy before and after surgery, and half had the immunotherapy drug durvalumab as well [1].
- In the final results, patients who also had durvalumab lived longer [1].
- It had already been seen that with this combination the tumour was completely gone in the tissue removed at surgery much more often (almost three times as often), and the disease came back less often [2].
- This treatment was approved in the US in November 2025 for stomach cancer that can be removed with surgery.
- Overall survival: how long patients lived.
- Progression-free survival: how long the disease did not get worse.
- Disease-free or event-free survival: how long the disease did not come back after treatment.
- Median: the number that half of patients were above and half below; for example, "a median of 10 months" means that in half of patients the disease stayed under control for at least 10 months.
- Phase 3: a large, careful study comparing a new drug with the usual treatment; the basis of most approvals.
Talk to your doctor about what this result means for you.
What does this finding mean for patients?
In some countries, such as Iran, stomach cancer is one of the most common and deadliest cancers [6]. This study shows that in stomach cancer that can be removed with surgery, adding an immunotherapy drug to chemotherapy before and after surgery helps patients live longer [1]. Talk to your doctor about whether it is right for you (stomach cancer).
What was reported?
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Perioperative FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin and docetaxel) has been the standard treatment for locally advanced gastric cancer since 2019; in the FLOT4 trial this regimen increased median survival to 50 months vs 35 months with the previous regimen [3]. Even so, recurrence rates remain high [2].
In the global, double-blind, placebo-controlled MATTERHORN trial at 147 centres in 20 countries, 948 patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (stage II to IVA) were randomised to durvalumab + FLOT or placebo + FLOT [1]. The first report (NEJM, 2025) showed 2-year event-free survival of 67.4% vs 58.5% and a pathological complete response rate of 19.2% vs 7.2% [2].
The final overall survival results have now been published in The Lancet: overall survival was significantly better in the durvalumab group. The investigators described this combination as "a new standard treatment option" for these patients [1].
In some countries, such as Iran, stomach cancer is one of the most common cancers, especially in men [6]. If your stomach cancer can be removed with surgery and you are going to have FLOT chemotherapy before and after the operation, this study shows that adding the immunotherapy drug durvalumab (a drip into a vein once every 4 weeks) can lower the chance of the cancer coming back and help you live longer [1, 2]. Adding this drug did not lead to more delays in surgery [2]. Talk to your doctor about whether this treatment is right for you.
Trial details and regimen (for physicians)
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- In the initial report, the hazard ratio for death was 0.99 in the first 12 months and 0.67 from month 12 onwards; that is, the curves separated late [2].
- Grade 3 or 4 adverse events were similar in the two groups (71.6% vs 71.2%), and the rate of surgical delay was 10.1% vs 10.8% [2]. Possibly treatment-related deaths occurred in 6 patients in the durvalumab group and 2 in the placebo group [1].
- This result contrasts with the KEYNOTE-585 trial (perioperative pembrolizumab), which did not meet its primary endpoint; the differences in design and endpoints are discussed in a JCO commentary [5].
MATTERHORN regimen (FDA label)
Durvalumab + FLOT before and after surgery, then durvalumab
Resectable gastric or gastro-oesophageal junction adenocarcinoma (stage II to IVA)
Resectable gastric or gastro-oesophageal junction adenocarcinoma (stage II to IVA)
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Each 4-week cycle | |||
| Durvalumab | 1500 mg (weight below 30 kg: 20 mg/kg) | IV infusion over 60 minutes, before chemotherapy | Day 1 |
| FLOT | |||
| Docetaxel + oxaliplatin + leucovorin | 50 + 85 + 200 mg/m² | IV | Days 1 and 15 |
| Fluorouracil | 2600 mg/m² | 24-hour continuous infusion | Days 1 and 15 |
| Maintenance | |||
| Single-agent durvalumab | 1500 mg | IV over 60 minutes | Every 4 weeks |
Durvalumab dose and schedule from the FDA label [7]; FLOT doses as in the FLOT4 trial [3]. Infuse through a 0.2 or 0.22 micron filter. Dose reduction of durvalumab is not recommended; immune-related adverse events are managed by withholding or discontinuing and corticosteroids [7].
Evidence: FLOT4 (2019)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Limitations and next steps
- In the US this treatment has been approved for cancer of the stomach, or of the place where the stomach joins the food pipe, that is removed with surgery: before and after surgery together with chemotherapy, and then on its own.
- Most patients in the study were men [1].
- The extra time patients lived is modest [1, 2].
- Approval: on 25 November 2025 the FDA approved durvalumab with FLOT as treatment before and after surgery, followed by single-agent durvalumab, for resectable gastric or gastro-oesophageal junction adenocarcinoma (FDA announcement).
- Most patients were men and the study focused on adenocarcinoma [1].
- The survival gain is modest [1, 2].
The main study
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Key study
1 itemPerioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer
References
7 referencesShow all references, 6 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.
- 1Perioperative 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
- 2
- 3Perioperative 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
- 4Adding durvalumab to perioperative FLOT improves gastric cancer outcomes
- 5KEYNOTE-585 Fails While Matterhorn Succeeds in Gastric Cancer: What Lessons Can We Learn?
- 6Cancer incidence in Iran in 2014: Results of the Iranian National Population-based Cancer Registry
- 7
This page is based on reputable scientific sources and was last updated on 28 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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