Role of the alpha-fetoprotein response in immune checkpoint inhibitor-based treatment of patients with hepatocellular carcinoma

Purpose: The dynamics of serum alpha-fetoprotein (AFP) level have been found to be a useful predictor of therapeutic responsiveness in patients with hepatocellular carcinoma (HCC). We evaluated whether AFP changes were able to accurately reflect imaging-based responses and predict prognosis in patients receiving therapies including immune-checkpoint inhibitors (ICIs). Methods: A total of 108 HCC patients with baseline serum AFP ≥ 20 ng/mL who received ICI-based treatment were included. We evaluated AFP-based responses, coupled with radiographic responses by RECIST, at 6–10 (time-point 1, TP1) and 14–18 weeks (time-point 2, TP2) of therapy in terms of the change of AFP from baseline, with a > 20% decrease or increase in level corresponding to the AFP response and progression, respectively. We examined the correlations between AFP and imaging-based responses, and the prognostic implications of the AFP-based measure. Results: Based on AFP change, there were 24 and 20 responders and 74 and 24 progressors at TP1 and TP2, respectively. The AFP responders yielded radiological objective responses in 90.9% (10/11) and 93.8% (15/16) of the cases at TP1 and TP2, respectively, compared with only 1.4% and none, respectively, of the AFP progressors at the corresponding times. The agreement between progression by RECIST and increased AFP level at the two time-points was 93.8% and 95.0%, respectively. The accuracy of the AFP-based criterion for predicting radiologic response/progression was comparable at TP1 and TP2. Both “AFP responder” and “AFP progressor” at TP1 or TP2 independently predicted the overall survival of patients (adjusted hazard ratios [95% confidence intervals], 0.360 [0.174–0.743] and 0.315 [0.117–0.850]; and 2.525 [1.362–4.679] and 3.908 [1.563–9.769], respectively). Conclusion: Our study suggests that on-treatment AFP changes can complement imaging findings and provide prognostic information for evaluating patients with AFP-producing HCC treated with ICI-based regimens.