Imfinzi Plus FLOT Significantly Improves Overall Survival in Gastric and Gastroesophageal Cancer

AstraZeneca has shared new, positive data from the Phase III MATTERHORN clinical trial (NCT04592913) evaluating Imfinzi (durvalumab) in combination standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy. This latest readout shows the combination demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of overall survival (OS) compared to chemotherapy alone.¹

Key overall survival results

Further results from the final OS analysis show:

• Imfinzi plus FLOT perioperative regimen reduced the risk of death by 22% versus chemotherapy alone (HR 0.78; 95% CI: 0.63–0.96; P=0.021).
• Median OS was not reached in either treatment arm.
• At three years, estimated survival was 69% with the Imfinzi-based regimen compared with 62% for FLOT alone.

In a press release, Josep Tabernero, MD, PhD, head of the Medical Oncology Department at the Vall d'Hebron University Hospital and director of the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, Spain, and principal investigator in the trial, said: “The MATTERHORN data are transformative for patients with early gastric and gastroesophageal cancers, where recurrence is common and long-term prognosis remains poor despite curative-intent surgery and chemotherapy. Nearly seven in 10 patients treated with the durvalumab-based perioperative regimen were alive at three years, and the survival benefit was observed regardless of PD-L1 status. With results like these, this novel treatment should become the new standard of care in this curative-intent setting.”

Pathologic outcomes and event-free survival

Additionally, AstraZeneca shared results from another analysis of the association between pathologic outcomes and event-free survival (EFS) in MATTERHORN.

• Pathologic response correlated with improved EFS in patients treated with Imfinzi versus the comparator.
• Hazard ratios for EFS by pathologic outcome were: Pathologic complete response (pCR) HR 0.29 (95% CI: 0.08–0.96), major pathologic response (MPR) HR 0.32 (95% CI: 0.15–0.68), and any pathologic response HR 0.60 (95% CI: 0.46–0.79).
• EFS benefit with Imfinzi was observed regardless of lymph node status at surgery (no nodal involvement HR 0.74; 95% CI: 0.46–1.18; nodal involvement HR 0.77; 95% CI: 0.58–1.02).

Trial design and methodology

The MATTERHORN trial is a randomized, double-blind, placebo-controlled, multi-center, global study evaluating Imfinzi as perioperative therapy in resectable Stage II-IVA gastric and gastroesophageal junction (GEJ) cancers.

• Perioperative treatment included both neoadjuvant and adjuvant therapy.
• A total of 948 patients were randomized to receive Imfinzi1500 mg plus FLOT chemotherapy or placebo plus FLOT every four weeks for two cycles before surgery.
• Following surgery, patients received Imfinzi or placebo every four weeks for up to 12 cycles, including two cycles with FLOT chemotherapy and 10 cycles as monotherapy.
• The trial’s primary endpoint was EFS, with key secondary endpoints including pCR rate and OS.

Earlier interim findings on event-free survival

Earlier in June, an interim analysis of MATTERHORN revealed that Imfinzi plus standard-of-care chemotherapy demonstrated a significant improvement in EFS in patients with resectable gastric and GEJ cancers. According to trial investigators, data from this analysis marked Imfinzi as the first immunotherapy to achieve statistically significant EFS in a global Phase III trial in this patient population.²

Results from this interim analysis of MATTERHORN showed:

• The two-year EFS rate was 67.4% with the Imfinzi combination versus 58.5% with placebo (HR 0.71; 95% CI: 0.58–0.86; P<0.001).
• The two-year OS rate was 75.7% for the Imfinzi group and 70.4% for the placebo group.
• Piecewise analysis showed a hazard ratio for death of 0.99 (95% CI: 0.70–1.39) during the first 12 months and 0.67 (95% CI: 0.50–0.90) after 12 months.

References

1. IMFINZI® (durvalumab)-based regimen reduced the risk of death by 22% in early gastric cancer vs. chemotherapy alone in MATTERHORN Phase III trial. News release. AstraZeneca. October 17, 2025. Accessed October 17, 2025. https://www.businesswire.com/news/home/20251017239598/en/IMFINZI-durvalumab-based-regimen-reduced-the-risk-of-death-by-22-in-early-gastric-cancer-vs.-chemotherapy-alone-in-MATTERHORN-Phase-III-trial

2. Phase III MATTERHORN Trial Shows Imfinzi Combo Significantly Improves Event-Free Survival in Resectable Gastric and GEJ Cancers. Applied Clinical Trials. June 4, 2025. Accessed October 17, 2025. https://www.appliedclinicaltrialsonline.com/view/matterhorn-trial-imfinzi-survival-resectable-gastric-gej-cancers