{"title":"Practice-Changing Trials in Gastrointestinal Cancers at ASCO 2025: A Critical Review and Clinical Context.","authors":"Nabil Ismaili","doi":"10.1080/07357907.2026.2654136","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9463,"journal":{"name":"Cancer Investigation","volume":" ","pages":"700-706"},"PeriodicalIF":2.2000,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/07357907.2026.2654136","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/4/10 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Cancer Investigation is one of the most highly regarded and recognized journals in the field of basic and clinical oncology. It is designed to give physicians a comprehensive resource on the current state of progress in the cancer field as well as a broad background of reliable information necessary for effective decision making. In addition to presenting original papers of fundamental significance, it also publishes reviews, essays, specialized presentations of controversies, considerations of new technologies and their applications to specific laboratory problems, discussions of public issues, miniseries on major topics, new and experimental drugs and therapies, and an innovative letters to the editor section. One of the unique features of the journal is its departmentalized editorial sections reporting on more than 30 subject categories covering the broad spectrum of specialized areas that together comprise the field of oncology. Edited by leading physicians and research scientists, these sections make Cancer Investigation the prime resource for clinicians seeking to make sense of the sometimes-overwhelming amount of information available throughout the field. In addition to its peer-reviewed clinical research, the journal also features translational studies that bridge the gap between the laboratory and the clinic.
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