Effect of Early Tumor Shrinkage and Depth of Response on the Clinical Outcomes of Patients with Unresectable Hepatocellular Carcinoma Treated with Transcatheter Arterial Chemoembolization and Lenvatinib plus PD-1 Inhibitors

INTRODUCTION: Systematic therapies, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), have now been approved as the mainstay treatment for patients with unresectable hepatocellular carcinoma (uHCC). However, only a minority of the patients are expected to respond to TKIs and ICIs. Because early tumor shrinkage (ETS) and depth of response (DoR) might have the potential to predict survival outcomes, this study aimed to identify the optimal cutoffs for ETS and DoR to predict patients' clinical outcomes in their early treatment stage. METHODS: This retrospective study enrolled patients with uHCC treated with triple combination therapy of transcatheter arterial chemoembolization (TACE) and lenvatinib plus toripalimab between November 2017 and March 2022. The clinical characteristics, ETS, DoR, and overall efficacy were collected to analyze the optimal cutoffs for ETS and DoR and predict patient survival outcomes. RESULTS: A total of 157 patients were included. The objective response rate (ORR) and disease control rate (DCR) were observed in 94 (59.87%) and 130 (82.8%) patients, respectively, with a median progression-free survival (mPFS) of 8 months and a median overall survival (mOS) of 23 months. Patients with ETS ≥10% had significantly longer mPFS (11 months) and mOS (24 months), and patients with DoR ≥27% had significantly prolonged mPFS (10 months) and mOS (23 months). CONCLUSION: ETS of 10% and DoR of 27% were identified as the optimal cutoffs for predicting the clinical outcomes of patients with uHCC treated with TACE and lenvatinib plus a programmed death-1 inhibitor.