Gastroesophageal Cancers — Year in Review Series on Relevant New Datasets and Advances

Gastroesophageal cancer management increasingly relies on precise biomarker assessment—specifically MSI-high status, HER2, PD-L1, and Claudin 18.2—to guide therapeutic selection. In locally advanced MSI-high disease, dual checkpoint inhibitor therapy demonstrates high pathologic complete response rates, suggesting potential for non-operative management. The Matterhorn study confirms that perioperative FLOT chemotherapy combined with durvalumab improves outcomes, establishing a new standard for patients who can tolerate triplet regimens. For HER2-positive cases, the bispecific antibody zanidatumab shows superior efficacy in combination with chemotherapy and immunotherapy, while trastuzumab deruxtecan has become the preferred second-line treatment. Despite these advances, clinicians must prioritize aggressive antiemetic protocols and careful monitoring for toxicities like interstitial lung disease. Ongoing research into bispecifics and antibody-drug conjugates continues to refine treatment strategies, shifting the focus toward more personalized, effective, and tolerable care pathways.