Exploring Early Kinetic Profiles of CEA, ctDNA and cfDNA in Patients With RAS-/BRAF-Mutated Metastatic Colorectal...

Area of Science:

• Oncology
• Molecular Diagnostics
• Clinical Trials

Background:

• Metastatic colorectal cancer (mCRC) patients exhibit varied responses to first-line chemotherapy.
• Early identification of non-responders can facilitate timely second-line therapy initiation.
• Carcinoembryonic antigen (CEA) is the current standard blood marker for mCRC monitoring.

Purpose of the Study:

• To explore the early kinetics of CEA, cfDNA, and ctDNA during first-line chemotherapy in mCRC.
• To investigate the association of these markers with treatment response, PFS, and OS.
• To evaluate ctDNA as a potential surrogate for oncological outcomes.

Main Methods:

• Analysis of 40 RAS-/BRAF-mutated mCRC patients from the NORDIC-VII trial.
• Development of a model to assess early on-treatment kinetics (e.g., percentage change, slope, AUC).
• Correlation of marker dynamics with radiological response and survival endpoints.

Main Results:

• Early ctDNA dynamics, particularly at day 49 (P49) and slope (S49), correlated with radiological response and PFS.
• ctDNA showed faster and more pronounced changes than CEA.
• Failure to achieve molecular ctDNA response by week 8 was associated with significantly shorter PFS and OS.

Conclusions:

• Early ctDNA dynamics during first-line chemotherapy possess prognostic value in mCRC.
• Suggests prospective validation of a ctDNA-based RECIST framework in clinical practice.
• Highlights ctDNA's potential as a sensitive biomarker for treatment response and outcomes.