Key Updates From MATTERHORN: Perioperative Durvalumab + FLOT in GC/GEJC

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The MATTERHORN trial represents a logical evolution in gastric cancer (GC) and gastroesophageal junction cancer (GEJC) treatment, building upon successful strategies from metastatic disease where checkpoint inhibitors have demonstrated survival benefits. The rationale follows the established oncology principle of moving effective therapies from advanced disease settings to earlier-stage, curative-intent treatment approaches. This phase 3 trial specifically investigated whether adding durvalumab, an anti–PD-L1 checkpoint inhibitor, to the established FLOT perioperative chemotherapy regimen could improve outcomes for patients with resectable GC and GEJC. The study design addressed a clear clinical question: Can immunotherapy enhance the current best standard of care represented by FLOT?

The MATTERHORN trial design was straightforward and methodologically sound, using FLOT as the control arm and testing the addition of durvalumab during both neoadjuvant and adjuvant phases, followed by extended durvalumab monotherapy maintenance. The primary end point was event-free survival, with overall survival analysis planned for later reporting. The trial successfully met its primary end point with clear, clinically meaningful results showing approximately an 8-percentage point improvement in 24-month event-free survival rates with the addition of immunotherapy to standard FLOT therapy.

The positive results of MATTERHORN represent a significant advancement in the treatment landscape for GC and GEJC. The trial demonstrated not only statistical significance but also clinical meaningfulness, with improved pathologic response rates and downstaging of tumors. These findings establish a new foundation for perioperative treatment that clinicians can build upon for future therapeutic advances. The clean design and clear results make this a practice-changing study that addresses the persistent challenge of suboptimal cure rates in these aggressive malignancies, offering renewed hope for improved patient outcomes through the integration of immunotherapy with established chemotherapy regimens.