Precision Antibody Therapy in Gastric and Gastroesophageal Cancer: Targeting FGFR2b, CLDN18.2, and VEGFR2

TL;DR

This paper reviews precision antibody therapies targeting FGFR2b, CLDN18.2, and VEGFR2 for gastric and gastroesophageal cancers, highlighting their clinical benefits and challenges.

Contribution

The paper provides a comprehensive review of three precision antibody therapies and their impact on treatment strategies for gastric and gastroesophageal cancers.

Findings

Bemarituzumab, Zolbetuximab, and Ramucirumab show clinically meaningful survival benefits in phase II–III trials.

Biomarker-driven selection improves efficacy but faces challenges like resistance and access.

These therapies represent a shift from chemotherapy to personalized, targeted treatments.

Abstract

Precision-targeted antibodies are transforming treatment for GI cancers.Bemarituzumab (FGFR2b), Zolbetuximab (CLDN18.2), and Ramucirumab (VEGFR2) demonstrate clinically meaningful survival benefits in phase II–III trials.Biomarker-driven patient selection enhances efficacy but poses challenges related to resistance and access.Integration of precision antibody therapy requires balancing clinical benefit, cost, and equitable implementation in oncology practice.

Precision-targeted antibodies are transforming treatment for GI cancers.

Bemarituzumab (FGFR2b), Zolbetuximab (CLDN18.2), and Ramucirumab (VEGFR2) demonstrate clinically meaningful survival benefits in phase II–III trials.

Biomarker-driven patient selection enhances efficacy but poses challenges related to resistance and access.

Integration of precision antibody therapy requires balancing clinical benefit, cost, and equitable implementation in oncology practice.

Gastric and gastroesophageal junction (G/GEJ) adenocarcinomas remain among the most aggressive and lethal malignancies globally. Most patients are diagnosed at advanced stages and respond poorly to conventional chemotherapy, highlighting the urgent demand for more effective, novel treatment strategies such as monoclonal antibody therapies targeting drivers of tumor progression. This review examines the mechanisms, safety profiles, and clinical trial outcomes of three targeted agents—bemarituzumab, zolbetuximab, and ramucirumab—which inhibit tumor growth through the FGFR2b, CLDN18.2, and VEGFR2 pathways, respectively. We also compare traditional versus adaptive clinical trial designs, explore emerging challenges such as therapeutic resistance and treatment-related toxicities, and consider implications for personalized medicine. Collectively, these agents represent a paradigm shift from empiric chemotherapy toward biomarker-driven immunotherapy, with the potential to significantly improve survival and quality of life in patients with advanced G/GEJ cancers.

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