Overview
Survival rates from gastric and gastroesophageal (GEJ) cancer remain poor in the United States as the disease is often diagnosed at a late stage and early detection continues to be a major challenge for healthcare professionals. Guidelines now recommend testing for multiple biomarkers (HER2, PD-L1, MMR/MSI, CLDN18) to personalize first-line treatment; yet, these tests are not being done consistently in real-world practice. Real-world evidence remains limited regarding whether patients receive guideline-recommended care based on multiple actionable biomarkers and how their clinical outcomes compare to those receiving non-concordant treatment. .
Researchers analyzed data from nearly 3,800 patients with advanced gastric or GEJ cancer with EHR activity between 2011-2025 and the start of 1L between September 1, 2017 and May 1, 2025. Testing rates varied across biomarkers: HER2 (78%), MMR/MSI (58%), PD-L1 (50%), and CLDN18 (only 6%). Among patients tested for multiple biomarkers, 13% had two or more actionable biomarkers. Concordance between biomarker results and treatment selection was high for HER2-positive disease (62% received HER2-directed therapy) but lower for PD-L1-positive and CLDN18-positive disease (less than 37% received IO or targeted treatment). When patients received non-concordant therapy, they had a 16% increased risk of progressing to the next treatment or death in the first 20 months after receiving first-line treatment.
Why this matters
These findings reveal important gaps in precision cancer care for gastric and GEJ cancers. While HER2-directed therapy is commonly used when biomarker testing is positive, many patients with other actionable biomarkers don't receive targeted treatments—even when evidence supports them. The study highlights the need for more comprehensive biomarker testing and clearer clinical guidance on how to prioritize between multiple positive biomarkers to advance precision medicine in these cancers.