Biomarker Testing and Key Subgroups in Gastric and GEJ Cancer
Key Points
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Next-generation sequencing (NGS) is crucial in gastric or gastroesophageal junction (GEJ) cancers, as treatment decisions are based on microsatellite instability (MSI), mismatch repair (MMR), PD-L1, claudin 18.2 (CLDN18.2), and HER2 statuses.
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Two novel targeted agents, zanidatamab and zolbetuximab, showed promising results in HER2–positive and HER2–negative populations, respectively.
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Circulating tumor DNA (ctDNA) status alone does not seem predictive enough to inform treatment changes, though ctDNA changes may warrant more frequent monitoring for progression.
Standards of Care in Unresectable Upper Gastrointestinal Cancers
Medical oncologists, Ajinkya Buradkar, MD, of Roswell Park Comprehensive Cancer Center, and Meghana Singh, MD, of West Virginia University Cancer Institute, sat down at an event coinciding with the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) to discuss the role of NGS in patients with unresectable, advanced gastric or GEJ cancers.
NGS testing at baseline is crucial for this disease group because all treatment decisions are informed by biomarker status, said Dr. Singh. Key subpopulations include MSI–high, MMR–deficient, HER2–positive, PD-L1–positive, and CLDN18.2–positive disease. Based on these markers, patients are indicated for various combinations of immunotherapy, chemotherapy, and targeted agents.
The doctors then reviewed two key developments in targeted therapies presented at ASCO GI. Firstly, the phase 3 HERIZON-GEA-01 trial reported that zanidatamab plus chemotherapy and tislelizumab improved progression-free and overall survival compared with standard trastuzumab plus chemotherapy in HER2–positive disease. Second, the phase 2 ILUSTRO trial showed that zolbetuximab achieved promising results when combined with chemotherapy and nivolumab in HER2–negative, CLDN18.2–positive patients.
With either novel targeted therapy, oncologists must counsel patients on expected toxicities and how to utilize supportive medications. Efficacy is important, but maintaining quality of life is essential, especially for advanced, unresectable disease populations, Dr. Singh said.
The doctors also briefly considered the role of circulating tumor DNA (ctDNA) in the treatment of gastric or GEJ cancer. Given the current data, Dr. Singh is hesitant to adjust treatment solely based on ctDNA, although she may perform more frequent monitoring if ctDNA status changes. This paradigm could change as more data become available, she noted.