medwireNews: Incorporating durvalumab into the standard perioperative FLOT regimen significantly boosts event-free survival (EFS) in people with resectable gastric or gastroesophageal junction (GEJ) cancer, indicate phase 3 data.
The risk for an event or death was reduced by a significant 29% with the addition of the PD-L1 inhibitor, researcher Yelena Janjigian (Memorial Sloan Kettering Cancer Center, New York, USA) told delegates of the 2025 ASCO Annual Meeting in Chicago, Illinois, USA.
And although the final overall survival analysis is pending, the data at this interim analysis “are encouraging,” she added.
The presenter continued: “MATTERHORN supports the global adoption of perioperative durvalumab plus FLOT as a new standard for patients with localized gastric and gastroesophageal junction adenocarcinoma.”
The study was launched because although FLOT chemotherapy given before and after surgery improves survival in these patients, “recurrences remain common,” explained Janjigian.
A total of 948 patients with untreated stage II–IVa gastric or GEJ cancer were enrolled from centers in Asia, Europe, North America, and South America. They were randomly assigned to receive durvalumab 1500 mg or placebo, given on day 1 of each 4-week cycle, alongside FLOT, which was given on days 1 and 15, for two neoadjuvant and two adjuvant cycles, followed by durvalumab at the same dose or placebo for a further 10 postoperative cycles.
At a median follow-up of 31.4–31.6 months, the primary endpoint of EFS was significantly improved with the addition of durvalumab to FLOT, with the median duration unreached versus 32.8 months with FLOT alone.
The EFS rate at 18 months was 73% in the durvalumab plus FLOT group versus 64% in the FLOT alone group, while at the 24-month mark the rates were 67% and 59%, respectively.
Janjigian reported that “the overall survival curves begin to separate at 12 months, with sustained separation thereafter.”
The hazard ratio for death of 0.78 numerically favored the addition of durvalumab, but “has not yet reached statistical significance,” and “the follow-up for overall survival is ongoing,” she added.
Turning to the safety data, the investigator noted that the “findings were consistent with the known profile of FLOT and durvalumab,” with grade 3–4 treatment-related adverse events occurring in a nearly identical 60% and 59% of patients in the durvalumab and placebo arms, respectively. The most common of these events in both groups was neutropenia, experienced by a respective 21% and 22% of participants.
Thirty percent of patients given durvalumab plus FLOT discontinued any study treatment due to toxicity, as did 23% of those given FLOT alone.
Discussant Samuel Klempner (Massachusetts General Hospital, Boston, USA) said that “the MATTERHORN trial moves the field forward and establishes perioperative durvalumab plus FLOT as the new standard for this patient population.”
He continued: “While overall survival is immature, I’m very optimistic that MATTERHORN will show a statistical improvement in overall survival based on the shape of the curves, the strong statistical design, and observations from other phase 3 perioperative gastric trials like RESOLVE and PRODIGE, where longer follow-up improved the hazard ratio and enhanced the significance of the p value.”
These results appeared simultaneously in The New England Journal of Medicine.
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2025 ASCO Annual Meeting; Chicago, Illinois, USA: 30 May–3 June
N Engl J Med 2025; doi:10.1056/NEJMoa2503701