Interpreting MATTERHORN: Perspectives on Perioperative Durvalumab + FLOT in GC/GEJC

Video content above is prompted by the following:

The MATTERHORN trial results represent a practice-changing advancement, with durvalumab plus FLOT (D-FLOT) poised to become the new standard of care for patients with resectable gastric and gastroesophageal adenocarcinomas who are surgical candidates. Although pathologic complete response (pCR) has faced criticism as a surrogate end point due to conflicting data from different studies, the MATTERHORN results are compelling because they demonstrate improvement in event-free survival alongside enhanced pathologic responses. Unlike previous studies with pembrolizumab that showed improved pCR without survival benefit, MATTERHORN used a different study design with FLOT as the backbone, making cross-trial comparisons inappropriate. The combination of improved pCR and event-free survival provides confidence in the clinical significance of this regimen.

The applicability of D-FLOT appears broad across patient subgroups, with data showing consistent benefits across multiple demographic and clinical categories presented in the trial. The main exception would be patients with MSI-H tumors, who already have excellent treatment options with checkpoint inhibitor combinations like ipilimumab and nivolumab without requiring chemotherapy. For most patients with microsatellite-stable tumors, D-FLOT represents the optimal therapeutic approach. The patient population studied in MATTERHORN closely mirrors typical clinical practice, with predominantly node-positive, locally advanced patients who face the highest risk of distant failure and would benefit most from enhanced systemic therapy.

The positive trial results have generated immediate clinical enthusiasm, with oncologists already planning to incorporate D-FLOT into practice as soon as access becomes available. The consistent data across subgroups and the meaningful clinical benefit observed provide confidence for broad implementation. Although overall survival data remains immature, the early trends appear promising, and most clinicians feel comfortable adopting this approach based on the robust event-free survival benefit. The MATTERHORN population’s characteristics align well with typical clinical practice, making the results highly applicable to real-world patient care scenarios.