Clinical trialPhase 3Stomach cancerOesophageal 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

The Lancet · 2026948 randomised patients (of 1258 patients enrolled in the study); 474 patients in each group

Janjigian YY, Al-Batran SE, Wainberg ZA, Muro K, Molena D, Van Cutsem E, et al. The Lancet. 2026. 408:1114-1128

Study type: Clinical trial
Study name: MATTERHORN
Phase: Phase 3
Design: Global, randomised, double-blind, placebo-controlled, multicentre trial (147 treatment centres in 20 countries in Asia, Europe, North America and South America)
Sample size: 948 randomised patients (of 1258 patients enrolled in the study); 474 patients in each group
Source: The Lancet · 2026
Trial registration: NCT04592913

In plain words

In this large study, patients with stomach cancer or cancer where the stomach meets the oesophagus that could be removed by surgery were given FLOT chemotherapy before and after the operation, together with either the immunotherapy drug durvalumab or a placebo. Patients who received durvalumab lived longer overall. Deaths possibly related to treatment were few in both groups (6 people in the durvalumab group and 2 in the placebo group). The decision about this treatment should be made with the treating doctor, based on each patient's situation.

Key results

Hazard ratio 0.78 (95% CI 0.63–0.96) in favour of durvalumab

Overall survival (OS) in the ITT population

P=0.021; significance threshold P<0.0499

6 (1%) of 475 patients vs 2 (less than 1%) of 469 patients

Death from an adverse event possibly related to study treatment

Durvalumab group vs placebo group

Drugs in this study:Docetaxel (Taxotere)Fluorouracil (5-FU)Oxaliplatin (Eloxatin)Durvalumab (Imfinzi)

Dose and schedule cards

Durvalumab + FLOT (MATTERHORN trial)

Resectable adenocarcinoma of the stomach or gastroesophageal junction, stage II to IVA (AJCC 8th edition), ECOG 0–1, no active autoimmune diseaseOn the page “Stomach cancer” · Localized resectable disease: perioperative and adjuvant therapy

Resectable adenocarcinoma of the stomach or gastroesophageal junction, stage II to IVA (AJCC 8th edition), ECOG 0–1, no active autoimmune disease

Drug	Dose	Route	Schedule
Before surgery: 2 cycles
Durvalumab	1500 mg (body weight less than 30 kg: 20 mg/kg)	IV	Day 1
FLOT	Standard FLOT doses (regimen above)	IV	Days 1 and 15
After surgery: 2 cycles
Durvalumab	1500 mg (body weight less than 30 kg: 20 mg/kg)	IV	Day 1
FLOT	Standard FLOT doses (regimen above)	IV	Days 1 and 15
Maintenance: up to 10 cycles
Durvalumab	1500 mg (body weight less than 30 kg: 20 mg/kg)	IV	Day 1

Cycle length: Every 28 days (FLOT every 14 days, i.e., days 1 and 15 of each cycle)
Duration: 2 cycles before surgery; after surgery, 2 cycles with FLOT followed by durvalumab monotherapy for up to 10 cycles (a maximum of 12 cycles in total after surgery)

Durvalumab dose and schedule from the FDA label; in the MATTERHORN trial, event-free survival and overall survival were improved. The doses of the individual FLOT components are not stated separately in the label or the abstracts; the standard FLOT4 doses serve as the basis.

On the page “Stomach cancer” · Localized resectable disease: perioperative and adjuvant therapy

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.

Treatment arms and regimens

1Durvalumab + FLOT

Durvalumab 1500 mg IV on day 1 of each 4-week cycle, with IV FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) on days 1 and 15 of each cycle, for 4 cycles (2 cycles before surgery and 2 cycles after surgery); then durvalumab 1500 mg IV every 4 weeks for 10 additional cycles (a maximum of 12 cycles after surgery in total).

According to the FDA label, for weight below 30 kg the durvalumab dose is 20 mg/kg. The doses of the individual FLOT components are not stated in the abstract or the FDA label (standard FLOT doses in the FLOT4 trial: docetaxel 50, oxaliplatin 85, leucovorin 200 and fluorouracil 2600 mg/m² as a 24-hour infusion).

2Placebo + FLOT

IV placebo on day 1 of each 4-week cycle with FLOT on days 1 and 15 of each cycle for 4 cycles (2 cycles before and 2 cycles after surgery); then placebo every 4 weeks for 10 additional cycles.

Source of the regimen details: Abstract of the paper (Lancet 2026) and the FDA label for Imfinzi (sections 2.2 and 14: schedule of durvalumab and FLOT on days 1 and 15 of each 4-week cycle); the doses of the FLOT components are not stated in the sources available for this trial, and the doses given are those of the FLOT4 trial

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults with histologically confirmed resectable gastric or gastro-oesophageal junction adenocarcinoma (suitable for radical surgery; stage II to IVa) who had not previously received any anticancer treatment. Median age was 62 years (interquartile range 54–68); 682 (72%) were men and 266 (28%) women.

Endpoints

The primary endpoint, reported previously, was event-free survival (EFS). Overall survival (OS) in the intention-to-treat (ITT) population was the key secondary endpoint and is the main endpoint of the present report. Safety data were collected during treatment and follow-up (up to 90 days after the last dose of study drug) and analysed in patients who received at least one dose of study treatment; these data were reported previously and are summarised here.

Safety and side effects

Adverse events leading to death and possibly related to any study treatment occurred in 6 (1%) of 475 patients in the durvalumab group and 2 (less than 1%) of 469 patients in the placebo group. Other safety data were reported previously and are not detailed in the abstract.

Clinical significance and place in guidelines

Based on these results, adding durvalumab to perioperative FLOT improved overall survival in resectable gastric and gastro-oesophageal junction adenocarcinoma, and the authors consider it a new standard treatment option. The status of regulatory approvals and clinical guideline recommendations should be checked separately, because the abstract does not mention them.

Limitations

The abstract does not report numerical event-free survival results by pathological response. The study is still ongoing and the safety data in this report are a summary of previously published data. Other limitations should be checked in the full text of the paper.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.