Imfinzi with FLOT Boosts Survival

Patients were treated with neoadjuvant Imfinzi in combination with chemotherapy before surgery, followed by adjuvant Imfinzi in combination with chemotherapy, then Imfinzi monotherapy. The trial evaluated this regimen versus perioperative chemotherapy alone for patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers. For the secondary endpoint of overall survival (OS), a strong trend was observed in favour of the Imfinzi-based regimen at this interim analysis. The trial will continue to follow OS, which will be formally assessed at the final analysis.

Gastric cancer is the fifth leading cause of cancer death globally, with nearly one million people diagnosed each year. In 2024, there were roughly 43,000 drug-treated patients in the US, European Union (EU) and Japan in early-stage and locally advanced gastric or GEJ cancer. Approximately 62,000 patients in these regions are expected to be newly diagnosed in this setting by 2030.

Yelena Y Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York and principal investigator in the trial, said: “Despite receiving curative-intent chemotherapy and surgery, patients with gastric cancer commonly face disease recurrence and have a poor prognosis. These exciting data from MATTERHORN show that a durvalumab-based perioperative regimen resulted in a clinically meaningful improvement in patient outcomes, including decreasing the risk of the cancer coming back.”

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “MATTERHORN is the first Phase III trial of an immunotherapy to show a statistically significant improvement in event-free survival in patients with resectable gastric and gastroesophageal junction cancers. This perioperative approach with Imfinzi underscores our commitment to moving into earlier stages of cancer where novel therapies can have the biggest impact on patients’ lives.”

The safety profile for Imfinzi and FLOT chemotherapy was consistent with the known profiles of each medicine, and there were no new safety findings. In a previously reported interim analysis for the key secondary endpoint of pathologic complete response (pCR), the Imfinzi combination more than doubled the pCR rate compared to neoadjuvant chemotherapy alone (19% versus 7%, odds ratio 3.08; p<0.00001). Data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

MATTERHORN is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage II-IVA gastric and GEJ cancers. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 948 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus FLOT chemotherapy or placebo plus FLOT chemotherapy every four weeks for two cycles prior to surgery. This was followed by Imfinzi or placebo every four weeks for up to 12 cycles after surgery (including two cycles of Imfinzi or placebo plus FLOT chemotherapy and 10 additional cycles of Imfinzi or placebo monotherapy).

In the MATTERHORN trial, the primary endpoint is EFS, defined as the time from randomisation until progression that precludes surgery or requires non-protocol therapy, local or distant recurrence or progression of disease, or death due to any cause as assessed by blinded independent central review (BICR) according to RECIST 1.1 and/or local pathology testing. Key secondary endpoints include pCR rate, defined as the proportion of patients who have no detectable cancer cells in resected tumour tissue following neoadjuvant therapy, and OS. The trial enrolled participants in 176 centres in 20 countries, including in the US, Canada, Europe, South America and Asia.