Optimizing treatment sequencing in hepatocellular carcinoma: Impact of radioembolization timing and immune checkpoint inhibitors on survival outcomes.

e16275 Background: The optimal sequencing of available locoregional therapies and systemic treatments for patients with hepatocellular carcinoma (HCC) remains uncertain. This study compared the impact of transarterial radioembolization (TARE) as a first-line (FL) versus second-line or subsequent-line (SL) treatment and examined the role of immune checkpoint inhibitors (ICIs) within these treatment sequences. Methods: A single center retrospective review was conducted evaluating patients with HCC receiving at least one TARE treatment between 1/2015 and 8/2022. Patient clinical and pathological characteristics were elucidated. The Kaplan–Meier method was used to estimate overall survival (OS; from diagnosis to death or loss to follow-up) and TARE-specific OS (OS-TARE; from TARE procedure to death or loss to follow-up). Results: In this cohort of 141 patients, the median age was 65 (range: 49-88); they were predominantly Caucasian (80%), male (80%), and Child-Pugh class A (75%). Fifty-nine patients (42%) had FL TARE and only 39 (28%) had ICI at some point (five before TARE). Baseline characteristics such as age, tumor characteristics, liver function, and prior therapy were comparable between FL and SL groups, except for a higher incidence of portal vein tumor thrombosis (PVTT) in the FL group (49% vs. 6%, p < 0.01) and lower rates of hepatic encephalopathy (19% vs. 37%, p = 0.02). Survival analysis is summarized below. While FL TARE showed improved OS-TARE compared to SL, the OS appeared numerically longer in the SL group (not significant). The addition of ICI in patients after TARE in FL improved survival while only OS-TARE improved in the SL group. Conclusions: Early use of TARE (FL) may provide survival benefits directly related to the procedure (OS-TARE), but overall outcomes are influenced by disease burden including the presence of PVTT. The addition of ICIs is associated with improved survival outcomes (both OS and OS-TARE), emphasizing their role as a critical component in the treatment strategy for HCC. Optimizing the sequencing of TARE and ICIs appears to play an essential role in improving outcomes, and future randomized controlled trials should further investigate this element of the HCC treatment paradigm. Survival analysis of patients with HCC managed with TARE with or without ICI. Survival FL vs. SL (p) ICI not received vs. received, (p) FL sub-group SL sub-group OS* 558 vs. 901(0.06) 401 vs. 1,102 (0.01) 887 vs. 1,080 (0.2) OS-TARE* 502 vs. 239 (0.024) 353 vs. 1,028 (0.02) 202 vs. 627 (0.001) *in days.