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Among patients with gastric/gastroesophageal junction (G/GEJ) adenocarcinoma that is resectable, Imfinzi with FLOT improved survival.
Among patients with gastric/gastroesophageal junction (G/GEJ) adenocarcinoma that is resectable, or removable by surgery the combination of the anti-PD-L1 monoclonal antibody Imfinzi (durvalumab) with the FLOT (5-fluorouracil-leucovorin-oxaliplatin-docetaxel) chemotherapy regimen was associated with a significant and clinically meaningful improvement in overall survival, or the time patients live after treatment, when compared to placebo plus FLOT.
These findings, which were regardless of pathological status, were shared in a presentation of data from the phase 3 MATTERHORN trial at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
With a data cutoff date of Sept. 1, 2025, the final overall survival analysis of the intention-to-treat population yielded a hazard ratio (HR) of 0.78 comparing the investigational arm with the control arm, with median OS not reached in either arm.
Overall Survival (OS): The length of time from the start of treatment or diagnosis that patients in a study are still alive.
Event-Free Survival (EFS): The length of time patients remain alive without certain events occurring, such as the cancer coming back, progressing, or death from any cause.
Pathological Complete Response (pCR): This means that when the tissue removed during surgery is examined under a microscope, no signs of invasive cancer are found.
“The overall survival results of the MATTERHORN study strongly support the use of Imfinzi plus chemotherapy with FLOT as a new global standard of care for patients with localized, [resectable, G/GEJ] adenocarcinoma,” said Dr. Josep Tabernero, professor of medicine, head, Department of Medical Oncology, Vall d’Hebron University Hospital, and director of Vall d’Hebron Institute of Oncology, Barcelona, Spain, in his presentation.
Furthermore, a survival analysis stratified by demographic and clinical characteristics showed that OS improvement was consistent across most key subgroups. Notably, a similar improvement in OS was achieved regardless of PD-L1 status. In patients who were PD-L1-positive, the HR was 0.79, and the HR was 0.79 in patients who were PD-L1-negative, even demonstrating identical HRs across groups.
Additional findings reported included an improvement in event-free survival (EFS), the study’s primary end point, among patients with any degree of pathological response and regardless of pathological nodal status at the time of the data cutoff on Dec. 20, 2024.
The phase 3 MATTERHORN trial is a global, randomized, double-blind, placebo-controlled study evaluating the efficacy of neoadjuvant-adjuvant durvalumab plus FLOT chemotherapy. The study’s primary end point is EFS; key secondary end points include OS and pathological complete response (pCR).
The study population consists of 948 patients with localized G/GEJ adenocarcinoma who were treatment-naive upon enrollment. Patients were enrolled from across Asia, Europe, North America and South America; of note, according Tabernero, is that 20% of patients were from Asia. Patients were stratified by geographical region, clinical lymph node status and PD-L1 expression.
For treatment, patients were randomly assigned to receive either the Imfinzi and FLOT combination or placebo plus FLOT (474 patients, both arms) in the neoadjuvant setting. Here, patients received their 1500 mg of their assigned treatment plus FLOT for two cycles before undergoing surgical resection four to eight weeks after their last dose. Following surgical resection recovery, patients received 1500 mg of durvalumab or placebo as adjuvant therapy for up to one year.
What Trial Data Have Been Previously Reported?
In 2023, interim results with a data cutoff on Feb. 1, 2023 suggested a significant and clinically meaningful benefit in pCR and near-PCR, with response rates of 27% and 14% observed in the investigational and control arms, respectively. Next, earlier in 2025, results of a primary end point analysis published in The New England Journal of Medicine revealed a two-year EFS rate of 67.4% in the investigational arm versus 58.5% in the control arm. A consistent and manageable safety profile between arms was depicted in both reports.
Riding on the favorable efficacy and safety trends observed in previous analyses, this most recent readout highlights the potential of durvalumab and FLOT to become a new perioperative treatment option for patients.
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