MATTERHORN: Building on Foundational Chemotherapy Regimens

Yelena Janjigian, MD, gastrointestinal medical oncologist at Memorial Sloan Kettering Cancer Center in New York, NY, discusses the phase 3 MATTERHORN clinical trial (NCT04592913), highlighting how its data builds upon previous research. She points to studies like ESOPEC (NCT02509286) and other "top care" studies, which have established the importance of chemotherapy with fluoropyridines and platinums in the metastatic setting.

A key point Janjigian emphasizes is the superiority of FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) in early-stage disease compared to CROSS, a regimen involving carbo-taxel radiation. She states that FLOT has consistently proven to be the most effective systemic treatment in the perioperative setting, surpassing outdated regimens.

The MATTERHORN trial, therefore, advances this understanding by demonstrating that FLOT combined with durvalumab (Imfinzi) improves outcomes compared to FLOT alone. Janjigian notes that the control arm in MATTERHORN (which received FLOT alone) actually showed better results than historical FLOT data. This suggests a growing comfort and proficiency among clinicians in administering FLOT, and that patients in the trial were able to complete most of the neoadjuvant and adjuvant FLOT treatments.

Janjigian frames MATTERHORN as building upon other triplet regimen studies. However, she places studies like KEYNOTE-585 (NCT03221426) in a different category because they utilized outdated doublet chemotherapy regimens with cisplatin, which has largely been replaced. She suggests that taxanes and oxaliplatin are more immunogenic and likely represent a better optimal therapy, especially for fit patients in the neoadjuvant setting.