Early Alpha-fetoprotein Response Associated With The Efficacy And Prognosis In Advanced Hepatocellular Carcinoma Treated With Lenvatinib

Background and purpose:Lenvatinib has been available as one of newly first-line target therapies for unresectable hepatocellular carcinoma(HCC),but lack of predictive and prognostic biomarkers.Alpha-fetoprotein(AFP)is the most widely used tumor marker for HCC.The value of prediction and prognosis of AFP response has been confirmed in different treatments of HCC.This retrospective study aims to investigate the effect of early AFP response on efficacy and prognosis in patients with unresectable HCC treated with lenvatinib.Methods:The unresectable HCC patients(AFP≥20 ng/ml)that received lenvatinib for≥1month between November,2018 and November,2020 were included in the analysis.Early AFP response was defined as >20% decrease in the level of AFP serum from baseline after 4 weeks of lenvatinib treatment.Radiological response was assessed using Response Evaluation Criteria in Solid Tumors criteria(RECIST)1.1.We compared radiological response,progression free survival(PFS)and overall survival(OS)between early AFP responders and AFP nonresponders.Potential prognostic factors for PFS and OS were analyzed using univariate and multivariate Cox regression models.Effect of early AFP response on PFS and OS were also assessed in specific subgroups.Results:1.Early AFP responders(N=21,53.8%),compared with nonresponders(N=18,46.2%),had significantly higher disease control rate(DCR),longer PFS and OS.DCR,85.7% vs 44.4%,P=0.015;median PFS,11.4 months vs 3.9 months,P=0.001;median OS,16.4 months vs 7.3 months,P=0.042.2.In multivariate analysis,early AFP nonresponse(HR=3.533,95%CI:1.441-8.659,P=0.006),together with ECOG PS 1(HR=3.423,95%CI: 1.300-9.011,P=0.013)and higher AST level(HR=1.014,95%CI: 1.001-1.027,P=0.029)was identified as an independent risk factor of PFS.Early AFP nonresponse(HR=5.451,95%CI:1.595-18.627,P=0.007),larger tumor diameter(HR=1.133,95%CI:1.002-1.281,P=0.046),ECOG PS 1(HR=3.827,95%CI:1.103-13.286,P=0.035)and ALBI grade 2(HR=12.010,95%CI:2.276-63.363,P=0.003)were independent risk factors of OS.3.PFS and OS in AFP responders versus nonresponders were assessed by age(≥60 vs <60 years),Barcelona Clinic Liver Cancer(BCLC)stage(B vs C),albumin-bilirubin(ALBI)grade(1 vs 2),cirrhosis(yes vs no),and treatment setting of lenvatinib(first-line vs second-or later-line).A trend towards benefit in PFS and OS was observed with early AFP response across most subgroups.Conclusion:1.Early AFP responders had significantly higher DCR,longer PFS and OS compared with AFP nonresponders.2.Early AFP response was an independent prognostic factor for HCC patients and can predict the survival of HCC patients treated with lenvatinib.3.The PFS and OS benefit in early AFP responders was consistent in HCC patients treated with lenvatinib across most subgroups.