Early alpha-fetoprotein response predicts prognosis of immune checkpoint inhibitor and targeted therapy for hepatocellular carcinoma: a systematic review with meta-analysis

BackgroundThe prognostic value of alpha-fetoprotein (AFP) response for efficacy of targeted therapy or immune checkpoint inhibitors (ICIs) has not been established. The purpose of this meta-analysis is to elucidate the relationship between AFP response and survival outcomes in hepatocellular carcinoma (HCC) patients who received targeted therapy or ICIs.MethodsThe hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the relationship between AFP response and overall survival (OS)/progression-free survival (PFS).ResultsTwenty-six articles containing 3056 HCC patients were finally included in the study. The pooled results showed that after targeted therapy or ICIs, patients with decrease in AFP had better prognosis (OS:HR = 0.48, 95%CI:0.40-0.56; PFS:HR = 0.39, 95%CI:0.33-0.46), while patients with increase in AFP had worse prognosis (OS:HR = 2.30, 95%CI:1.82-2.89; PFS:HR = 2.34, 95%CI = 1.69-3.24). Subgroup analysis revealed that compared to AFP decrease >50%, AFP decrease >20% can better predict the prognosis of patients who received targeted therapy (OS:HR = 0.51, 95%CI:0.41-0.62; PFS:HR = 0.39, 95%CI:0.30-0.51) or ICIs treatment (OS:HR = 0.34, 95%CI:0.16-0.71; PFS:HR = 0.22, 95%CI:0.10-0.47), and 8 weeks after targeted therapy may be the appropriate time point for AFP assessment.ConclusionAFP decrease >20% within 8 weeks may be the appropriate definition for early AFP response which probably works best in predicting the efficacy of therapy.RegistrationThe review was not registered.

Automated summary

This meta-analysis examined the relationship between alpha-fetoprotein (AFP) response and survival outcomes in hepatocellular carcinoma (HCC) patients treated with targeted therapy or immune checkpoint inhibitors (ICIs). The results showed that AFP decrease was associated with better prognosis, while AFP increase was associated with worse prognosis. Furthermore, a decrease in AFP greater than 20% within 8 weeks may be the appropriate definition for early AFP response in predicting therapy efficacy.