MATTERHORN Spotlight—Shaping the Treatment Horizon for Gastric/Gastroesophageal Junction (GEJ) Cancers

Sam Klempner, MD; Michael K. Gibson, MD, PhD; Kaitlyn Kelly, MD, MAS; and Nataliya Uboha, MD, PhD, discuss how the positive results from the phase 3 MATTERHORN trial, which demonstrated that adding durvalumab to perioperative FLOT chemotherapy significantly improved event-free survival in patients with resectable gastric and gastroesophageal junction cancers, establishes a new standard of care that they plan to implement in clinical practice while addressing practical considerations around patient selection, multidisciplinary coordination, and managing the toxicity profile of this combination regimen.

EP. 1: Understanding GC/GEJC: Disease Overview and Current Treatment Practices

June 25th 2025

Panelists discuss how gastric cancers (GC) and gastroesophageal junction cancers (GEJC) present with nonspecific symptoms, affect approximately 1.2 million patients worldwide annually, and are managed with perioperative FLOT chemotherapy as the established standard of care for resectable disease.

EP. 2: Perioperative Therapy In GC/GEJC: Challenges and Unmet Needs

June 25th 2025

Panelists discuss how perioperative FLOT chemotherapy has simplified treatment decisions but presents toxicity challenges for patients with comorbidities, while emphasizing the critical importance of laparoscopic staging and acknowledging that current approaches still fail to cure approximately half of patients.

EP. 3: Key Updates From MATTERHORN: Perioperative Durvalumab + FLOT in GC/GEJC

July 2nd 2025

Panelists discuss how the MATTERHORN trial successfully demonstrated that adding durvalumab immunotherapy to perioperative FLOT chemotherapy significantly improved event-free survival with an 8-percentage point improvement at 24 months, representing a clear advancement in the treatment paradigm.

EP. 4: Interpreting MATTERHORN: Perspectives on Perioperative Durvalumab + FLOT in GC/GEJC

July 2nd 2025

Panelists discuss how the MATTERHORN results represent a practice-changing advancement that they are ready to implement clinically, with improved pathologic complete response rates and event-free survival providing confidence in the regimen’s efficacy across most patient subgroups except those with microsatellite instability–high (MSI-H) tumors.

EP. 5: Surgical Considerations With IO In Perioperative GC/GEJC

July 11th 2025

Panelists discuss how adding immunotherapy (IO) to perioperative chemotherapy does not appear to complicate surgical procedures or compromise the ability to achieve negative margins, with R0 resection rates remaining unchanged between treatment arms in the MATTERHORN trial.

EP. 6: Checkpoint Inhibitors In GC/GEJC: Trials Across the Landscape

July 11th 2025

Panelists discuss how other immunotherapy trials in the perioperative setting, including studies with pembrolizumab and atezolizumab, have shown mixed results, with improved pathologic responses not necessarily translating to survival benefits. They note the negative results from the adjuvant CheckMate 577 trial.

EP. 7: Redefining the Standard: Impact of MATTERHORN on the GC/GEJC Landscape

July 18th 2025

Panelists discuss how MATTERHORN establishes durvalumab plus FLOT as the new standard of care for all patients with resectable gastric cancers (GC) and gastroesophageal junction cancers (GEJC) who are candidates for curative-intent surgery, with plans to implement this regimen immediately upon regulatory approval.

EP. 8: From Trial to Practice: Considerations for Delivering FLOT + IO to Patients

July 18th 2025

Panelists discuss how adding durvalumab to FLOT does not significantly increase toxicity profiles and can be safely delivered using standard oncology practices with appropriate dose modifications, nutritional support, and multidisciplinary care coordination.

EP. 9: Multidisciplinary Collaboration for Perioperative IO in GC/GEJC

July 25th 2025

Panelists discuss how successful implementation of durvalumab plus FLOT requires enhanced multidisciplinary coordination involving oncologists, surgeons, pharmacists, nurses, and nutritionists to optimize patient outcomes and manage the complexities of perioperative care.

EP. 10: Future of Perioperative IO + FLOT Chemotherapy in GC/GEJC

July 25th 2025

Panelists discuss how perioperative immunotherapy (IO) will serve as the foundation for future therapeutic advances, with potential directions including biomarker-driven personalized treatment, organ preservation strategies for complete responders, and integration of novel targeted therapies into the treatment paradigm.

EP. 11: Key Takeaways and Future Questions in Perioperative GC/GEJC

August 1st 2025

Panelists discuss the key takeaways, including the establishment of durvalumab plus FLOT as the new standard requiring proper laparoscopic staging and multidisciplinary care. Future questions focus on optimizing treatment for nonresponders and developing more personalized therapeutic approaches.

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