Gastric/GEJ- Phase III MATTERHORN

The MATTERHORN study is a recent, large Phase III clinical trial investigating the use of the immunotherapy drug durvalumab (Imfinzi) in combination with standard FLOT chemotherapy for patients with resectable early-stage and locally advanced gastric or gastroesophageal junction (GEJ) cancers. The trial included 948 participants and randomized them to receive either durvalumab plus FLOT or placebo plus FLOT during both pre-surgery (neoadjuvant) anad post-surgery (adjuvant) periods.
Key findings:
Event-free survival (EFS): The durvalumab plus FLOT group showed a statistically significant and clinically meaningful improvement in EFS compared to chemotherapy alone. At two years, 67.4% of patients in the durvalumab arm were event-free versus 58.5% with chemotherapy alone.
      •     Recurrence risk: The combination reduced the risk of disease progression, recurrence, or death by 29% compared to chemotherapy alone.
      •     Pathologic complete response: The combination more than doubled the rate of patients with no detectable cancer in resected tissue after neoadjuvant treatment in previous analyses.
      •     Overall survival (OS): A strong trend toward improved OS was observed, but this endpoint will be assessed in the final analysis.
      •     Safety: The regimen had a manageable safety profile.
Clinical significance:
      •     MATTERHORN is the first global phase III trial to prove that adding an immunotherapy (durvalumab) to perioperative chemotherapy for resectable gastric or GEJ cancer significantly improves outcomes over the current standard of care.
In summary, the MATTERHORN study demonstrates that perioperative treatment with durvalumab and FLOT chemotherapy enhances survival without recurrence or progression and could reshape management of early-stage and locally advanced gastric and GEJ cancers