Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma

Authors:
James Yu Division of Hematology and Medical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL

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and
Rutika Mehta Department of Oncology/Hematology, Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY

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 MD, MPH
Volume/Issue:
Volume 23: Issue 5
Online Publication Date:
May 2025
DOI:
https://doi.org/10.6004/jnccn.2025.7036
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The last 2 decades have seen a paradigm shift in the treatment landscape of metastatic gastric and gastroesophageal adenocarcinomas, with most of the progress occurring in recent years. Following the pivotal ToGA trial and the approval of trastuzumab for HER2-positive disease, the search for biomarkers has advanced exponentially. Currently, therapies are guided by key biomarkers such as HER2, PD-L1, dMMR/MSI-H, and, most recently, CLDN18.2. FGFR2b is emerging as a potential biomarker in this field. The most recent addition to this therapeutic arsenal is zolbetuximab. Two recent phase III trials have demonstrated survival benefits with the addition of zolbetuximab to frontline chemotherapy. A number of other biomarker-driven clinical trials are in progress, investigating new targeted agents that are expected to further transform the management of gastric or gastroesophageal adenocarcinoma.

Submitted November 4, 2024; final revision received March 7, 2025; accepted for publication March 10, 2025.

Disclosures: Dr. Mehta has disclosed serving as a scientific advisor for Arcus Biosciences, Bristol Myers Squibb, Merck, Eisai, Eli Lilly, AstraZeneca, Seagen, Novartis, Astellas, BeiGene, Legend Biotech, Guardant Health, BostonGene, Natera, GSK, and Amgen. Dr. Yu has disclosed having no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

Correspondence: Rutika Mehta, MD, MPH, Department of Oncology/Hematology, Weill Cornell Medicine/New York Presbyterian Hospital, 1305 York Avenue, 12th Floor, New York, NY 10021. Email: rum9028@med.cornell.edu
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Print ISSN:
1540-1405
Online ISSN:
1540-1413
Publisher:
National Comprehensive Cancer Network
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Copyright:
Copyright © 2025 by the National Comprehensive Cancer Network 2025
Article Category:
Review Article
Received:
04 Nov 2024
Accepted:
10 Mar 2025
Print Publication Date:
01 May 2025
Online Publication Date:
May 2025

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