AstraZeneca has received European Commission approval for Imfinzi (durvalumab) in combination with FLOT chemotherapy, a landmark achievement representing the first immunotherapy-based regimen to demonstrate survival benefits in early-stage gastric and gastroesophageal junction (GEJ) cancers. The approval, reported by PharmaBiz.com, addresses a critical clinical gap for approximately 15,500 EU patients annually treated for these devastating malignancies.
The European approval follows a rigorous review by the Committee for Medicinal Products for Human Use and is anchored by compelling data from the MATTERHORN phase III trial, published in The New England Journal of Medicine. This randomized, double-blind, placebo-controlled trial evaluated 948 patients with resectable, stage II-IVA gastric and GEJ cancers receiving perioperative therapy—treatment administered both before and after surgery.
Gastric cancer remains a global health crisis, representing the fifth leading cause of cancer death worldwide with nearly one million new diagnoses annually. Despite aggressive multimodal treatment involving surgery and chemotherapy, patients face disappointingly high recurrence rates and poor long-term outcomes. Historically, approximately one in four patients undergoing curative surgery develop recurrent disease within one year, with less than half surviving five years.
The MATTERHORN trial delivers transformative clinical evidence. In the planned interim analysis, the Imfinzi-FLOT perioperative regimen achieved a 29% reduction in disease progression, recurrence, or death compared to chemotherapy alone, translating to an event-free survival hazard ratio of 0.71. At one year, 78.2% of patients treated with the immunotherapy-based regimen remained event-free versus 74.0% in the chemotherapy-only group. This benefit persisted at 24 months, with 67.4% versus 58.5% event-free rates, respectively.
Most significantly, the final overall survival analysis demonstrated a statistically significant 22% reduction in death risk for the Imfinzi-FLOT combination compared to chemotherapy alone. An estimated 69% of patients in the immunotherapy arm survived three years compared to 62% receiving chemotherapy alone. Notably, survival curves showed increasing separation at subsequent time points, indicating the magnitude of benefit expands over time—a pattern suggesting durable immunologic effects.
The immunotherapy benefit appeared universal: an OS advantage was observed regardless of tumor PD-L1 expression status, expanding potential treatment eligibility. Safety data proved reassuring, with grade 3 or higher adverse events occurring in 71.6% of the Imfinzi-FLOT arm versus 71.2% in the comparison group. Critically, surgery completion rates were similar between groups, demonstrating that perioperative immunotherapy did not compromise surgical feasibility.
The regimen comprises two cycles of Imfinzi combined with FLOT chemotherapy administered preoperatively, followed by surgery, then additional Imfinzi-FLOT cycles and continued Imfinzi monotherapy up to 12 total post-operative cycles. This comprehensive perioperative approach addresses the disease’s aggressive natural history.
Josep Tabernero, principal investigator and Director of Vall d’Hebron Institute of Oncology, described the approval as transformative, establishing a new standard of care for early gastric and GEJ cancers. The EU approval marks AstraZeneca’s third perioperative Imfinzi-based regimen approval in Europe, reinforcing the company’s commitment to early-stage disease where curative intent remains possible.
Regulatory applications are advancing in Japan and other countries, with approval already granted in the United States. This milestone represents genuine progress for gastric cancer patients worldwide, offering the first immunotherapy-driven survival benefit in the perioperative setting and potentially reshaping treatment paradigms in this historically challenging malignancy.
