Early alpha-fetoprotein response predicts treatment efficacy of antiangiogenic systemic therapy in patients with advanced hepatocellular carcinoma.

Abstract

Antiangiogenic therapy has become the most important treatment modality for patients with advanced hepatocellular carcinoma (HCC). In this study, the authors investigated levels of alpha-fetoprotein (AFP) as a potential biomarker for treatment efficacy of antiangiogenic therapy. Patients with advanced HCC who had been enrolled in 3 prospective phase 2 clinical trials that evaluated either sorafenib, bevacizumab, or thalidomide in combination with a potentially antiangiogenic, metronomic, oral 5-fluoropyrimidine as first-line systemic therapy were included. An early AFP response was defined as a decline >20% from baseline after 2 to 4 weeks of treatment. AFP response was analyzed for its association with treatment efficacy and survival outcome. Seventy-two patients were included for early AFP response evaluation, and 12 of those patients (17%) were classified as early AFP responders. Early AFP responders, compared with nonresponders, had a significantly improved overall response rate (33% vs 8%; P=.037) and a significantly improved disease control rate (83% vs 35%; P=.002), which was defined as the percentage of patients who had an objective response plus stable disease for a minimum of 8 weeks. AFP responders, compared with nonresponders, also had longer median progression-free survival (PFS) (7.5 months vs 1.9 months; P=.001) and longer median overall survival (OS) (15.3 months vs 4.1 months; P=.019). In a multivariate analysis, AFP response remained a significant independent predictor of better PFS and OS. The current results indicated that an early AFP response is a useful surrogate marker to predict treatment response and prognosis in patients with advanced HCC who receive antiangiogenic therapy.