Early Alpha-foetoprotein Response Associated With Treatment Efficacy of Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma

Yu-Yun Shao; Tsung-Hao Liu; Chiun Hsu; Li-Chun Lu; Yin-Chung Shen; Zhong-Zhe Lin; Ann-Lii Cheng; Chih-Hung Hsu


Liver International. 2019;39(11):2102-2111. 

In This Article

Abstract and Introduction


Background: Post-treatment decline in serum alpha-foetoprotein (AFP) levels has been shown to predict the treatment efficacy of antiangiogenic therapy for advanced hepatocellular carcinoma (HCC). We explored whether a decline in AFP levels was also associated with treatment outcomes of immune checkpoint inhibitors (ICIs) in patients with advanced HCC.

Methods: We reviewed all patients who received ICI therapy for advanced HCC. AFP response was evaluated in patients with the pretreatment AFP level of >20 ng/mL. We defined early AFP response as a >20% decline in serum AFP levels within the first 4 weeks of treatment initiation relative to pretreatment levels. We then studied whether early AFP response was associated with treatment outcomes.

Results: Sixty patients were enrolled in this study; 43 of them were evaluable for early AFP response. The objective response rate of early AFP responders was significantly higher than that of early AFP nonresponders (73% vs. 14%, P < .001). Early AFP responders, compared with early AFP nonresponders, exhibited significantly longer overall survival (OS) (median, 28.0 vs 11.2 months, P = .048) and progression-free survival (PFS) (median, 15.2 vs 2.7 months, P = .002). After adjusting for other clinicopathological variables and treatments, early AFP response remained an independent predictor for longer OS (hazard ratio [HR] = 0.089, 95% confidence interval [CI] = 0.018–0.441; P = .003) and PFS (HR = 0.128, 95% CI = 0.041–0.399; P < .001).

Conclusion: Early AFP response was associated with higher treatment efficacy of ICIs for advanced HCC. Additional validation studies are nonetheless warranted.