Who is this for?
This is for people with stomach cancer or gastroesophageal-junction cancer (the adenocarcinoma type) that is removable by surgery — stage II to early stage IV, not yet spread to distant organs.
For this cancer, surgery offers the best chance of cure, but even after a successful operation it comes back in a large share of people. So treatment is given around the surgery to lower that risk — and this trial asked whether adding immunotherapy to that plan helps.
What kind of trial is this?
MATTERHORN was a global phase III randomized, double-blind, placebo-controlled trial — the most rigorous kind. It tested whether adding durvalumab to standard FLOT chemotherapy, around surgery, improved outcomes compared with FLOT plus a placebo.
Background: surgery plus chemo, and now immunotherapy
For resectable stomach and GEJ cancer, the standard has been chemotherapy (FLOT) before and after surgery — which improves cure rates but still leaves a high chance of recurrence. Immunotherapy had already proven itself in advanced stomach cancer, so the natural next step was to move it earlier, around surgery, where the immune system may have the best chance to wipe out any remaining cancer. This mirrors the same successful idea in other cancers — for example, the KEYNOTE-522 trial in breast cancer.
The trial: what was tested and how
MATTERHORN enrolled 948 people with resectable stomach or GEJ cancer, randomly assigned to one of two groups:
- Durvalumab + FLOT (474 people): standard FLOT chemotherapy plus durvalumab, before and after surgery, with durvalumab continuing afterward.
- FLOT + placebo (474 people): the same chemotherapy and surgery, without the immunotherapy.
The main measure was event-free survival — staying free of the cancer progressing, coming back, or death.
Results: what they found
Adding immunotherapy lowered the chance of recurrence and greatly increased how often the tumor was completely cleared — without adding meaningful side effects or delaying surgery.
Durvalumab + FLOT vs FLOT alone
Adding immunotherapy lowered the risk of the cancer coming back, progressing, or death by 29% (HR 0.71).
Nearly tripled the number of people whose removed tissue showed no living cancer — an early sign the treatment worked especially well.
Survival trended better, with the gap widening after the first year — though at this analysis it had not yet crossed the trial’s strict statistical bar, so longer follow-up is needed to confirm it.
Importantly, adding durvalumab did not increase serious side effects (grade 3+ in about 72% of both groups) or delay surgery — so the benefit came without a meaningful tolerability cost.
Why give immunotherapy before surgery, not just after?
Giving immunotherapy while the tumor is still in the body means the immune system can “see” the whole cancer and learn to recognize it — building an immune response that keeps working after the tumor is removed, to mop up any cells left behind. The high rate of tumors completely disappearing by surgery is a direct sign of that up-front effect. It’s the same logic behind perioperative immunotherapy in other cancers.
What is FLOT?
FLOT is a combination of four chemotherapy drugs (fluorouracil, leucovorin, oxaliplatin, and docetaxel), given before and after surgery. It has been the standard chemotherapy for resectable stomach and GEJ cancer because it improves cure rates over older regimens. MATTERHORN kept FLOT as the backbone and added immunotherapy on top.
The bottom line
For stomach and gastroesophageal-junction cancer removable by surgery, adding the immunotherapy durvalumab to standard FLOT chemotherapy — before and after the operation — lowered the chance the cancer came back (2-year event-free survival 67% vs 59%) and nearly tripled the number of people whose tumor had completely vanished by surgery (19% vs 7%). It did this without extra side effects or surgical delays. Overall survival is trending better and awaits longer follow-up, but this has established perioperative immunotherapy as a major step forward for this cancer.
What this could mean for you
- Immunotherapy is moving earlier. For resectable stomach/GEJ cancer, adding immunotherapy to chemotherapy around surgery is now a leading approach.
- The tumor may be gone by surgery. A complete response at surgery is a hopeful sign — and far more common with immunotherapy added.
- It doesn’t add much burden. Side effects and surgical timing were similar to chemo alone.
- Survival data are maturing. The recurrence benefit is clear; the longer-term survival benefit is still being confirmed.
Questions & comments
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