Abstract
Immune checkpoint inhibitors (ICIs) have emerged as first-line therapy for advanced-stage HCC with modest response rates (<33%). Combination treatments offer the potential to improve response rates while improving outcomes. This study evaluates the safety and outcomes of first-line Yttrium-90 plus ICI ((90)Y-ICI). A retrospective, multi-center study was conducted in HCC patients receiving first-line (90)Y-ICI with atezolizumab plus bevacizumab (Atezo/Bev) or tremelimumab plus durvalumab (Treme/Durva). Treatment response was evaluated at follow-up for planned (90)Y treatment cycle. Time-to-event measures of time to progression (TTP), progression-free survival (PFS), and overall survival (OS) served as primary endpoints, with first cycle response rates and AEs as secondary outcomes. This study included 37 patients receiving (90)Y-ICI from 2021 to 2024 (16-month median follow-up). The cohort was predominantly Child-Pugh A (92%) with HCV-related cirrhosis (67%), advanced stage (54%), and a median index HCC size of 8.0 cm (IQR: 6-12 cm). Grade 3-4 AEs occurred in six patients (16%). The target objective response (OR) rate was 83%, with a 50% target complete response (CR) rate. Overall OR was 61% with an overall CR of 39%. Median PFS was 11 months with 1-year rates of 50%. Patients with a target CR had improved TTP (p = 0.004), PFS (p = 0.003), and OS (p = 0.003). The cohort's 2-year OS was 41% with a median OS of 19 months (CI: 12-37 months). First-line (90)Y-ICI therapy in HCC is safe and effective, with no deviation in anticipated results. Patients achieving target CR showed significantly improved TTP, PFS, and OS, supporting target CR as an optimal treatment target.