AstraZeneca Durvalumab Regimen Demonstrates Survival Benefit in Early Gastric Cancer

The European Commission’s (EC) approval of AstraZeneca’s durvalumab (brand name Imfinzi) in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy, announced in March 2026, strongly demonstrates how the integration of immunotherapy into earlier-stage gastrointestinal cancers is accelerating. The trend is rising as perioperative treatment strategies begin to demonstrate durable survival benefits in resectable disease settings.¹

The EC’s approval of durvalumab plus FLOT chemotherapy is indicated for adult patients with resectable, early-stage and locally advanced gastric and gastroesophageal junction cancers. The regimen includes administration before and after surgery followed by maintenance monotherapy.

“This approval marks our third perioperative approval in Europe for an Imfinzi-based regimen, underscoring AstraZeneca’s commitment to transforming outcomes in early-stage disease, where cure is possible,” said Dave Fredrickson, executive vice president, Oncology Hematology Business Unit, AstraZeneca, in a company press release.¹ “For patients with early gastric and gastroesophageal cancers, this immunotherapy-based regimen delivers a durable survival benefit that increases over time.”

The approval is based on results from a Phase III trial (MATTERHORN), which demonstrated statistically significant improvements in both event-free survival (EFS) and overall survival (OS) compared with chemotherapy alone.² The decision follows a positive opinion from the Committee for Medicinal Products for Human Use.

How does perioperative immunotherapy improve outcomes in gastric cancer?

Despite curative-intent surgery and chemotherapy, recurrence rates in gastric and gastroesophageal cancers remain high, with a substantial proportion of patients experiencing disease progression within the first few years after treatment.³

In the Phase III trial, perioperative durvalumab combined with FLOT chemotherapy reduced the risk of disease progression, recurrence, or death by 29% compared with chemotherapy alone (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.58–0.86; p<0.001). Median EFS was not reached in the durvalumab arm versus 32.8 months in the comparator group.¹

Overall survival analysis demonstrated a 22% reduction in the risk of death (HR 0.78; 95% CI 0.63–0.96; p=0.021). At three years, an estimated 69% of patients receiving the durvalumab-based regimen were alive compared with 62% in the chemotherapy arm. Survival curves showed increasing separation over time, suggesting a durable treatment effect.¹

“Despite curative-intent surgery and chemotherapy, patients with resectable gastric and gastroesophageal cancers still face high recurrence rates and an urgent need for improved long-term survival,” said Josep Tabernero, MD, PhD, head of the Medical Oncology Department at Vall d'Hebron University Hospital and director of the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, Spain, and principal investigator in the Phase III trial, in the release.¹

“In MATTERHORN, nearly 70 per cent of patients were still alive three years after treatment with the durvalumab-based perioperative regimen. This EU approval brings patients the first immunotherapy regimen to extend survival in this early setting and is poised to become the new standard of care,” Dr. Tabernero added.

What role could perioperative checkpoint inhibition play in earlier-stage disease?

Durvalumab is a monoclonal antibody that targets programmed cell death ligand-1 (PD-L1) and is designed to block tumor immune evasion and enhance antitumor immune responses. Its application in perioperative settings reflects a broader shift toward introducing immunotherapy earlier in the disease course, where the potential for cure is highest.

The study enrolled 948 patients with Stage II–IVA gastric or gastroesophageal junction cancers across 176 global centers. Patients received durvalumab plus FLOT chemotherapy before surgery, followed by adjuvant therapy including continued durvalumab treatment. Clinical benefit was observed regardless of PD-L1 status, indicating potential applicability across a broad patient population.

Gastric cancer remains a leading cause of cancer mortality globally, with nearly one million new cases diagnosed annually. Recurrence following surgery continues to limit long-term survival, reinforcing the need for treatment strategies that extend beyond cytotoxic chemotherapy.⁴

As checkpoint inhibitors expand into perioperative settings across tumor types, these Phase III results provide further evidence supporting immunotherapy as a foundational component of early-stage cancer treatment paradigms.

References

1. AstraZeneca. Imfinzi approved in the EU as first and only perioperative immunotherapy for patients with early gastric and gastroesophageal cancers. Press Release. March 16, 2026.
2. AstraZeneca. Imfinzi regimen reduced risk of progression, recurrence or death by 29% in early-stage gastric cancer vs. chemotherapy alone in MATTERHORN Phase III trial. Press Release. June 1, 2025.
3. Li Y, Zhao H. Postoperative recurrence of gastric cancer depends on whether the chemotherapy cycle was more than 9 cycles. Medicine (Baltimore). 2022;101(5):e28620. doi: 10.1097/MD.0000000000028620
4. World Health Organization. International Agency for Research on Cancer. Stomach Fact Sheet. Accessed March 17, 2026. https://gco.iarc.who.int/media/globocan/factsheets/cancers/7-stomach-fact-sheet.pdf.