The U.S. Food and Drug Administration (FDA) has approved durvalumab (Imfinzi) in combination with chemotherapy for adults with certain types of stomach (gastric) or gastroesophageal junction (GEJ) adenocarcinoma that can be surgically removed. This marks a new treatment option for patients with early-stage, resectable disease.
At the ESMO Congress 2025 in Berlin, researchers shared final results from the global Phase 3 MATTERHORN trial (NCT04592913), confirming a major step forward in the treatment of patients with operable gastric and gastroesophageal junction (GEJ) adenocarcinoma.
The study evaluated durvalumab (Imfinzi), an immunotherapy that helps the immune system recognize and attack cancer, combined with standard FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel), compared with FLOT alone. The final results now show that adding durvalumab significantly improves overall survival, supporting the FDA approval of this combination.
What the Study Found
The MATTERHORN trial enrolled 948 patients with resectable, locally advanced gastric or GEJ cancer. Participants were randomly assigned to receive either:
- Durvalumab every four weeks plus FLOT chemotherapy (four preoperative and four postoperative cycles), followed by ten additional cycles of durvalumab alone, or
- A placebo plus the same FLOT chemotherapy schedule.
Key findings presented at ESMO 2025:
- Longer survival: Patients treated with durvalumab plus FLOT lived significantly longer than those who received chemotherapy alone. The improvement in survival was both statistically significant and clinically meaningful (HR 0.78; 95% CI 0.63–0.96; p=0.021).
- Broad benefit: The survival advantage was observed regardless of PD-L1 expression levels (a biomarker that sometimes predicts response to immunotherapy), with similar outcomes across all patient subgroups.
- Stronger tumor response: A greater number of patients who received durvalumab had no remaining cancer in their lymph nodes after surgery (58.2% vs 44.8%), suggesting a deeper treatment effect.
- Durable improvement: The event-free survival advantage seen in earlier analyses (measuring how long patients remain free of recurrence or progression) was reinforced in this final report.
- Manageable side effects: The addition of durvalumab did not delay surgery or recovery, and serious treatment-related side effects were similar between the two study groups.
Like other immunotherapies, durvalumab can cause immune-related side effects, including inflammation of the lungs, liver, intestines, and other organs. Patients also may experience infusion-related reactions or complications following stem cell transplantation.
What This Means for Patients
These results confirm that adding Imfinzi (durvalumab) to FLOT chemotherapy before and after surgery can improve long-term outcomes for people with gastric and GEJ cancer. The benefit applies broadly across patients, regardless of PD-L1 expression or nodal involvement, indicating that immunotherapy can enhance chemotherapy’s long-established curative role.
For patients newly diagnosed with resectable gastric or GEJ adenocarcinoma, these findings are highly encouraging. They suggest that immunotherapy may help reduce the risk of recurrence and extend survival after surgery.
Looking Ahead
With these results, durvalumab plus FLOT is emerging as a new global standard of care for patients with operable gastric and GEJ adenocarcinoma who are candidates for combination therapy. The MATTERHORN findings also reinforce a growing trend—bringing immunotherapy earlier into the cancer treatment timeline, even for patients with potentially curable disease.
If you or a loved one has been diagnosed with gastric or gastroesophageal junction cancer, talk with your oncology team about whether immunotherapy-based treatment may be appropriate.
More Reading:
Treatment and Management of Esophageal Cancer
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References
1. Hoeppner J, Brunner T, Schmoor C, et al. Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer. N Engl J Med. 2025 Jan 23;392(4):323-335.
2. https://pubmed.ncbi.nlm.nih.gov/35535555/
3. Tabernero J, et al. ESMO Congress 2025, Proffered Paper Session (LBA81).
