Objective:

To evaluate whether early dynamics of circulating tumor DNA predict efficacy and prognosis during fruquintinib treatment in patients with refractory metastatic colorectal cancer.

Approach:

Key Findings:

• Among 120 enrolled patients, 107 completed day-28 circulating tumor DNA testing.
• Day-28 dynamics showed clearance in 17.8% and a decrease in 43.9%.
• Clearance and decrease groups had higher disease control rates (adjusted odds ratios of 6.92 and 3.45; both P < 0.01) and lower progression risk (adjusted hazard ratios of 0.41 and 0.62; both P < 0.05).
• Adding circulating tumor DNA stratification improved model discrimination for progression-free survival (ΔC-index = 0.07) and overall survival (ΔC-index = 0.06).
• Common adverse events included hypertension (46.7%), hand-foot skin reaction (40.8%), and fatigue (36.7%).

Interpretation:

Limitations:

• Modest discriminative performance (C-index 0.69) indicates that prospective validation is required before clinical implementation.

Conclusion:

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