Assessment of Circulating Tumor DNA Burden in Patients With Metastatic Gastric Cancer Using Real-World Data

Area of Science:

• Oncology
• Molecular Diagnostics
• Biomarker Research

Background:

• Circulating tumor DNA (ctDNA) is an emerging biomarker in oncology.
• Gastric cancer (GC) shows potential for ctDNA's prognostic and predictive value.
• Real-world data (RWD) is crucial for validating biomarkers in clinical practice.

Purpose of the Study:

• To investigate the association between pretreatment ctDNA burden and clinical outcomes.
• To analyze first-line (1L) treated metastatic gastric cancer (mGC) patients in the US.
• To assess ctDNA's role as a prognostic biomarker in mGC.

Main Methods:

• Utilized the GuardantINFORM real-world clinical-genomic database.
• Included mGC patients tested with Guardant360 before 1L treatment (June 2014-March 2022).
• Classified ctDNA burden (high/low) using median variant allele fraction (MVAF); analyzed time to treatment discontinuation (rwTTD), time to next treatment (rwTTNT), and overall survival (rwOS).

Main Results:

• 824 mGC patients identified; 91% had detectable ctDNA (median MVAF 2.9%).
• In chemo-treated patients (n=537), high ctDNA burden correlated with shorter rwTTNT (4.8 vs 7.4 months) and rwOS (13.2 vs 19.1 months).
• No significant association found for immunotherapy or trastuzumab-based treatments.

Conclusions:

• High pretreatment ctDNA burden is linked to worse outcomes in 1L chemotherapy-treated mGC patients.
• ctDNA burden demonstrates potential as a prognostic biomarker for mGC.
• RWD analysis supports ctDNA's clinical utility in mGC management.