The ASCO 2025 meeting featured several phase III trials with the potential to impact gastrointestinal cancer management. CheckMate 577 reported mature overall survival (OS) data for adjuvant nivolumab in esophageal/GEJ cancer; however, OS benefit was not statistically significant in the intent-to-treat population and appeared restricted to PD-L1-positive tumors. MATTERHORN demonstrated significant improvements in event-free survival and OS with perioperative durvalumab plus FLOT in gastric/GEJ cancer. In stage III dMMR colon cancer, ATOMIC supported adjuvant atezolizumab plus chemotherapy, though questions persist about chemotherapy necessity and neoadjuvant immunotherapy. For advanced disease, BREAKWATER established encorafenib-based triplet therapy as first-line standard for BRAF V600E-mutant metastatic colorectal cancer, while DESTINY-Gastric04 confirmed trastuzumab deruxtecan as superior second-line therapy for HER2-positive gastric cancer, mandating re-biopsy. Given the great interest in circulating tumor DNA, we integrate the ESMO 2025 DYNAMIC-III trial, demonstrating ctDNA-guided de-escalation reduces toxicity with outcomes approaching standard care. These advances mandate comprehensive biomarker testing while highlighting persistent evidence gaps.
N. Ismaïli (Fri,) studied this question.