Association of early alpha-fetoprotein response with survival in patients with HBV-related hepatocellular carcinoma receiving lenvatinib.

Abstract

448 Background: Lenvatinib is a standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). We assessed the value of early alpha-fetoprotein (AFP) response for predicting clinical outcomes to lenvatinib treatment in patients with HBV-related uHCC and elevated AFP levels. Methods: This was a retrospective analysis of the medical records of consecutive patients with HBV-related uHCC and baseline AFP levels ≥20 ng/ml who received lenvatinib for > 1 month at The First Hospital of Jilin University between November 2018 and May 2021. Early AFP response was defined as a > 20% decrease in AFP serum level from baseline after 4 weeks of lenvatinib treatment. We evaluated radiological response using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as well as progression-free survival (PFS), and overall survival (OS) in AFP responders and non-responders. Potential prognostic factors for PFS and OS were assessed using univariate and multivariate Cox proportional hazards models. Intergroup differences were compared using a Mann–Whitney U test for continuous variables, a Fisher’s exact test for categorical variables and a log–rank test for survival data. Results: Medical records from 79 patients were screened and a total of 46 patients were included in the analysis; 84.4% had received lenvatinib in first-line, 63% were Child-Pugh class A, 56.4% had extrahepatic metastases, 35.6% had portal vein thrombosis and 10.3% and 87.2% had BCLC stage B and C disease, respectively. Of the 46 patients, 65.2% (n = 30) were early AFP responders and 34.8% (n = 16) were AFP non-responders. Baseline characteristics were balanced between early AFP responders and non-responders, except for age (≥60 years: 43.3% vs. 12.5%; p = 0.0366) and presence of portal vein thrombosis (46.7% vs. 13.3%; p = 0.0277). The median follow-up time was 18.0 (IQR, 3-29) months. Early AFP responders versus non-responders had a significantly higher objective response rate (34.5% vs 6.3%, p = 0.0349), disease control rate (82.8% vs 50.0%; p = 0.0203) and a longer median PFS (13.0 vs 7.0 months; HR, 0.464; 95% CI, 0.222-0.967; p = 0.028). Multivariate analysis confirmed that early AFP response (HR, 0.366; 95% CI, 0.169-0.795; p = 0.0110), ECOG PS of 0 (HR, 0.497; 95% CI, 0.323-0.877; p = 0.0326) and ALBI grade 1 (HR, 0.411; 95% CI, 0.277-0.863; p = 0.0283) were independent prognostic factors for longer PFS. Conclusions: AFP is an important prognostic factor and a predictive biomarker of survival benefit for patients with HBV-related uHCC receiving treatment with lenvatinib.