Redefining the Standard: Impact of MATTERHORN on the GC/GEJC Landscape

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The MATTERHORN trial establishes D-FLOT as the new standard of care for patients with resectable GC and GEJC, with immediate plans for clinical implementation once accessibility is achieved. The practice-changing nature of this positive trial means that essentially all patients intended for curative-intent surgery should be considered for this regimen, with the primary exception being those with microsatellite instability–high tumors who have excellent alternative treatment options. The MATTERHORN patient population closely mirrors typical clinical practice, featuring predominantly node-positive, locally advanced patients who represent the highest-risk group for distant failure and who would benefit most from enhanced systemic therapy targeting micrometastatic disease.

Implementing D-FLOT will require coordinated multidisciplinary care, emphasizing the critical importance of early multidisciplinary tumor board discussions at diagnosis. The regimen should be offered to any patient where curative-intent surgery is the goal, although patients who are never surgical candidates represent a different clinical question not addressed by MATTERHORN. The consistency of benefit across multiple subgroups in the trial data provides confidence for broad application, reinforcing that this represents a true advance in standard care rather than a niche treatment for selected patients.

Although the primary end point of event-free survival has been convincingly met, the anticipated maturation of overall survival data would further reinforce the clinical value of this approach. The early trends in overall survival curves appear promising, and most clinicians are comfortable implementing this regimen based on the robust event-free survival benefit alone. The trial's internal validity and design quality, combined with the meaningful clinical benefit observed, position D-FLOT as the foundation for future therapeutic development rather than a temporary bridge to better treatments. This represents a clear step forward in improving cure rates for these aggressive malignancies.