A perioperative immunotherapy combination has received a positive opinion from European regulators for patients with early-stage gastric and gastroesophageal junction (GEJ) cancers. 

The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use has recommended approval of Imfinzi (durvalumab, AstraZeneca), in combination with FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) as neoadjuvant and adjuvant therapy, followed by adjuvant Imfinzi monotherapy, for adults with resectable, early-stage or locally advanced gastric or GEJ adenocarcinoma.

Gastric and GEJ cancers have high recurrence rates despite curative-intent surgery with perioperative chemotherapy. About 1 in 4 patients experience recurrence within 1 year, and 5-year survival is less than 50%.

Durvalumab is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and triggering inhibition of immune responses.

Clinical Evidence and Trial Results 

The positive endorsement is based on survival data from the phase 3 MATTERHORN trial, which showed significant improvements in patient outcomes.

The study recruited 948 patients across 176 centers in 20 countries. It assessed durvalumab as perioperative treatment for patients with resectable stage II-IVA gastric and GEJ cancers. Patients received either 1500-mg fixed-dose durvalumab plus FLOT chemotherapy or placebo plus FLOT chemotherapy every 4 weeks for two cycles before surgery, followed by durvalumab or placebo every 4 weeks for up to 12 cycles after surgery.

In a planned interim analysis, patients treated with the durvalumab-based perioperative regimen demonstrated a 29% reduction in the risk for disease progression, recurrence, or death compared with chemotherapy alone. Estimated median event-free survival was not yet reached for the durvalumab arm vs 32.8 months for the comparator arm. An estimated 78.2% of patients treated with the durvalumab-based regimen were event-free at 1 year vs 74.0% in the comparator arm.

The final overall survival analysis revealed a significant and clinically meaningful survival improvement in which the durvalumab-based regimen reduced the risk for death by 22% compared to chemotherapy alone. An estimated 69% of patients treated with perioperative durvalumab plus FLOT were alive at 3 years compared with 62% in the placebo plus FLOT arm. An overall survival benefit was observed regardless of PD-L1 expression status.

Safety Profile and Regulatory Status 

The safety profile for durvalumab and FLOT chemotherapy was consistent with the known profiles of each medicine, and the percentage of patients that completed surgery was similar compared to chemotherapy alone.

Since the first approval in May 2017, more than 414,000 patients have been treated with Imfinzi. The drug is currently approved in the European Union to treat certain forms of non-small cell lung cancer, small cell lung cancer, biliary tract cancer, hepatocellular carcinoma, endometrial cancer, and muscle-invasive bladder cancer.

Detailed recommendations for the use of this product will be described in the Summary of Product Characteristics, which will be published on the EMA website after the marketing authorization has been granted by the European Commission.