ESMO GI 2025 | EFS and PRO data from the MATTERHORN study

At the congress this week we presented the results of the MATTERHORN study, specifically focusing on patient-reported outcomes. Of course, we know that 1.2 million people will die of gastric and gastroesophageal adenocarcinoma worldwide this year, so we need to do better. Metastatic disease, we already have chemoimmunotherapy for several years, but in early stage disease whether adding anti-PD-1 therapy to chemotherapy will improve outcomes is not yet known. So what we demonstrated with the MATTERHORN study, we looked at derolimab, an anti-PD-L1 agent, with modern three-drug chemotherapy of fluorouracil, lucavorin, oxaliplatin, and docetaxel, or the so-called FLOT regimen, in perioperative global study. This is the first study of this kind. and 948 patients were randomized in one-to-one fashion. These were early-stage non-metastatic tumors. Patients were enrolled globally in North America, Europe, South America, and Asia. And patients were randomized to receive durvalumab or placebo with FLOT before surgery, followed by surgery and additional treatment with up to a year of adjuvant therapy. At ASCO 2025 in the plenary session and in the NEJM publication we already demonstrated that FLOT is feasible globally and in fact it did not compromise addition of durvalumab to FLOT did not compromise surgery 92 percent of patients had complete resection in both arms more than nearly 100% got all perioperative cycles of FLOT, and more than half completed all standard adjuvant and experimental adjuvant therapy. So that was great. We also demonstrated an improvement in event-free survival, hazard ratio of 0.71, with 29% reduction in risk of death or progression of disease. And the median overall survival is trending positive, but the p-value was not yet mature so we need to follow up on that. What about FLOT? Will it be feasible? Well we demonstrated that it is and it doesn’t add you know durvalumab it does not add any new immune related adverse events. We knew you could have a slight increase in immune adverse events but the grade 3-4 toxicities with both regimens both durva FLOT or placebo with FLOT was approximately 59 and 60 percent So almost identical. But will the patients and how will the patient tolerate it? And so at ESMO this year, ESMO GI represented the patient reported outcomes and the quality of life measures. And it looks and it demonstrates that the patient-reported outcomes and the quality of life measures are equivalent in both arms. So most of the side effects that we see in patients comes with the chemotherapy. An addition of durvalumab does not negatively impact their outcomes and how they tolerate this regimen, which is, of course, very reassuring to see because it’s a practice-changing, global new standard. And so we want to be able to bring it to the patients worldwide and give them access to this regimen. Of course, there is some learning curve if the clinicians feel that FLOT may be difficult to administer. What we did see is that there’s a wide range of patients enrolling in the study. We had patients as young as 26, but also some patients in their 80s. And even in each subgroup analysis based on age, sex, geographic location, all of the groups favored addition of davrolumab, even patients with PD-L1 negative tumors. And so this is an important data to be aware of.