The U.S. Food and Drug Administration has approved Imfinzi (durvalumab) for use along with standard FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy to treat adults with early stages and resectable as well as locally advanced gastroesophageal junction (GEJ) or gastric cancers, including stages II, IVA, and III. This drug is manufactured by AstraZeneca. The treatment plan includes neoadjuvant Imfinzi+chemotherapy prior to surgery, followed by adjuvant Imfinzi with chemotherapy, and then Imfinzi monotherapy.
Gastric cancer is the world’s 5th most common and deadliest cancer. Nearly one million new cases and around 660,000 deaths were reported globally during 2022. These incidences are rising in people aged <50 years. Approximately 43,000 patients in Japan, the US, and the EU received drug treatment for early-stage or locally advanced gastric or GEJ cancer in 2024. This number may reach 62,000 by 2023. Recurrence is common, with one in four patients relapsing within a year and a low five-year survival rate, even with surgery and preoperative chemotherapy.
Imfinzi is a human monoclonal antibody that blocks PD-L1 from binding CD80 and PD-1. This helps restore anti-tumor immune responses. In gastrointestinal cancers, it is approved with chemotherapy for the treatment of biliary tract cancer and with Imjudo (tremelimumab) for unresectable hepatocellular carcinoma (HCC) and as monotherapy for HCC in the EU and Japan. Imfinzi is also a global standard for unresectable stage III non-small cell lung cancer (NSCLC) after chemoradiotherapy and is approved in multiple perioperative and metastatic NSCLC settings, as well as extensive- and limited-stage small cell lung cancer (SCLC). Beyond lung cancer, it is approved in advanced endometrial cancer and nonmuscle- and muscle-invasive bladder cancer. Over 414,000 patients have received Imfinzi.
This approval was granted after an FDA Priority Review, which is supported by results from the MATTERHORN trial. It was a multicentre (176 centers across 20 countries), double-blinded, placebo-controlled, randomized global phase III controlled clinical study. A total of 948 patients were randomly assigned to receive either Imfinz with FLOT or a placebo with FLOT. They received this treatment every 4 weeks for two cycles before surgery. After surgery, they continued with Imfinzi or a placebo every 4 weeks for up to 12 cycles. The primary endpoint was event-free survival (EFS). Secondary outcomes were overall survival (OS) and pathogenic complete response rate. Â
Imfinzi-based perioperative regimen reduced the risk of recurrence, disease progression, and death by 29% compared to chemotherapy alone, with EFS hazards ratio [HR] of 0.71 (95% confidence interval [CI] 0.58-0.86) and p<0.001. The estimated median EFS was reached with the Imfinzi group, but was 32.8 months with the comparator group. EFS rates were found to be 78.2% in the Imfinzi-based perioperative regimen arm compared to 74% in the control group at one year and 67.4% vs 58.5% at two years. OS results showed a 22% reduction in risk of death in Imfinzi and FLOT perioperative regimen compared to FLOT alone, with HR of 0.78 (95% CI 0.63-0.96) and p=0.021, as well as 3-year survival of 69% vs 62%. Similar safety outcomes were observed in both groups with respect to Grade ≥3 adverse events (71.6% vs 71.2% of patients).
AstraZeneca leaders and clinical experts said that Imfinzi, in combination with FLOT, offers a new standard treatment for early-stage and GEJ cancers, with survival benefits. Imfinzi marks the first neoadjuvant immunotherapy approval for these cancers, improving clinical outcomes and reducing recurrence in affected patients. U.S. submission was reviewed under Project Orbis, whereas this regimen is under review in Switzerland, Japan, Canada, the European Union, Australia, and other countries for the same indication.
Reference: AstraZeneca. Imfinzi approved in the US as first and only perioperative immunotherapy for patients with early gastric and gastroesophageal cancers. Published November 25, 2025. Accessed November 26, 2025. Imfinzi approved in the US as first and only perioperative immunotherapy for patients with early gastric and gastroesophageal cancers
