Gastric / GEJ Cancer · Medical Oncology · Perioperative

MATTERHORN: Perioperative durvalumab plus FLOT for resectable gastric and gastro-oesophageal junction adenocarcinoma

Treatment

Experimental: durvalumab 1500 mg IV every 4 weeks plus FLOT every 2 weeks (5-FU 2600 mg/m², leucovorin 200 mg/m², oxaliplatin 85 mg/m², docetaxel 50 mg/m²) for 4 cycles: 2 neoadjuvant and 2 adjuvant, followed by durvalumab 1500 mg IV every 4 weeks for 10 additional cycles. Total: 12 durvalumab cycles over approximately 1 year. Control received placebo on the same schedule plus FLOT.

Absolute Effect

• 3-year overall survival: 68.6% vs 61.9% — absolute improvement +6.7 percentage points; OS HR 0.78 (95% CI 0.63–0.96), P=.021.
• 2-year event-free survival: 67.4% vs 58.5% — absolute improvement +8.9 percentage points; HR 0.71 (95% CI 0.58–0.86), P<.001.
• Pathological complete response: 19.2% vs 7.2% — absolute improvement +12.0 percentage points.

NNT: approximately 15 for one additional patient alive at 3 years, and approximately 12 for one additional patient event-free at 2 years, based on the reported absolute differences.

Critical clinical review

MATTERHORN provides randomized phase III evidence that adding perioperative durvalumab to FLOT improves both event-free and overall survival in resectable gastric/GEJ adenocarcinoma. The absolute gains are clinically relevant, but the regimen adds immunotherapy, treatment duration and immune-related toxicity to an already intensive perioperative programme. The trial was not designed to isolate which treatment phase contributes the benefit.

Reference

Janjigian YY et al. Lancet. Published online 9 September 2026. DOI: 10.1016/S0140-6736(26)01254-7. NCT04592913.