Background: he role of serum alpha-fetoprotein (AFP) changes in predicting the treatment outcomes of advanced hepatocellular carcinoma (HCC) patients to sorafenib remains unknown.
Methods: Serum AFP was collected prospectively at baseline and subsequent follow-up visits in parallel with clinical and survival outcomes. AFP response was defined as a relative drop of AFP >20% of the baseline level after 6 weeks of sorafenib. The relationship between AFP response and the treatment outcomes was first explored in patients who received sorafenib in a phase II study. Subsequently, an independent validation set of patients were obtained to validate the association of AFP response to clinical outcomes.
Results: Included in the exploration and validation sets for analysis were 41 and 53 patients, respectively, with baseline AFP level >20 μg/L. In the exploration cohort, AFP response was significantly associated with clinical benefit (CB) rate (relative chance 3.4, 95% confidence interval [CI], 1.1-11.1), and multivariate analysis indicated that AFP response was associated with significantly better progression-free survival (PFS) (hazard ratio [HR], 0.31; 95% CI, 0.13-0.76) and marginally better overall survival (OS) (HR, 0.30; 95% CI, 0.09-1.02). When applying AFP changes in the validation set, significant associations were again found between AFP response with CB rate (relative chance, 5.5; 95% CI, 2.3-13.6) and PFS (HR, 0.12; 95% CI, 0.04-0.30) but not OS (HR, 0.61; 95% CI, 0.27-1.26).
Conclusion: Drop in AFP level at 6 weeks is an exploratory early surrogate for both CB and PFS in advanced HCC patients receiving sorafenib.