Durvalumab Boosts EFS in Resectable Gastric and GEJ Cancer
A recent trial reveals that durvalumab enhances event-free survival in patients with resectable gastric and gastroesophageal junction adenocarcinoma.
The phase 3 MATTERHORN trial (NCT04592913) presented at the 2025 ASCO Annual Meeting demonstrated that adding durvalumab (Imfinzi) to perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) significantly improves event-free survival (EFS) in patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma.
This global, randomized, double-blind, placebo-controlled study enrolled patients with stage II to IVa gastric or GEJ adenocarcinoma, without evidence of metastases and with an ECOG performance status of 0 or 1. Participants were randomized 1:1 to receive either durvalumab or placebo in addition to FLOT across neoadjuvant and adjuvant phases.
Treatment began with 2 cycles of neoadjuvant therapy, followed by surgery. Postoperatively, patients received 2 additional cycles of the combination, then up to 10 cycles of adjuvant monotherapy with durvalumab or placebo. Durvalumab was dosed at 1500 mg every 4 weeks throughout.
EFS, a growing standard end point in perioperative trials for gastroesophageal cancers, was the primary end point. Investigators define EFS events in advance—such as recurrence, progression, or death—and monitor patients accordingly.
"Event-free survival is generally a newer end point in gastroesophageal cancers, and it is commonly used in perioperative trials. Event-free survival is something you specify ahead of time in your study design about what will count as an event. And then you follow patients for events, and you, of course, tally the events between the arms and look at differences and timing to events,” explains Samuel Klempner, MD, gastrointestinal medical oncologist, Oncology, Massachusetts General Hospital and faculty, Medicine, Harvard Medical School, in an interview with Targeted OncologyTM.
The trial showed a statistically significant improvement in EFS for the durvalumab arm, with an approximately 8% absolute improvement at the 24-month landmark. This benefit establishes durvalumab plus FLOT as a potentially practice-changing regimen in the perioperative management of resectable gastric/GEJ adenocarcinoma.
Key secondary end points include overall survival, pathological complete response, and disease-free survival, which are still being analyzed. However, the clear EFS benefit supports the integration of immunotherapy into standard perioperative treatment.
“The study met its primary end point and concluded that durvalumab plus FLOT improved event-free survival in this population,” adds Klempner
