Real-world treatment patterns among U.S. adults with unresectable hepatocellular carcinoma (uHCC) eligible for locoregional therapy (LRT).
Authors: Kamble Shital , Ramakrishnan Karthik , Hurwitz Kathleen , Dubrovsky Leonid , Estenson Kasey , Hendrickson Kayla , Jackman Leah , Bowden Laney , Siegel Abby B. , Fried Michael 
Published: January 2025

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Background:
Treatment (tx) in uHCC has mostly relied on locoregional liver-directed tx, such as transarterial chemoembolization (TACE) or radioembolization (TARE), but recent pharmacotherapy advances have provided more tx options. This study aims to describe current real-world tx patterns and clinical outcomes of uHCC eligible for LRT.
Methods:
uHCC patients enrolled in TARGET-HCC (an ongoing, 5-year, longitudinal, observational cohort of HCC patients receiving usual care at academic and community sites in the U.S.), who initiated tx between 6/1/2020-6/1/2023 were included and followed until 12/31/2023 (data cutoff). Patients receiving curative HCC tx (ablation, resection, or transplant) or with metastatic HCC, portal vein involvement, or Child-Pugh-C liver disease at diagnosis (dx) were excluded. Patient and disease characteristics, and txs data were abstracted from electronic health records. Index tx was defined as first tx after dx, with a 30-day grace period for combination txs. Subsequent tx was defined as first tx after the grace period; for index systemic therapies, the subsequent tx differed from the index tx. Real-world progression-free survival (rwPFS) was defined as time from index tx to first event: radiological progression (including new lesions, extrahepatic involvement, vascular invasion, or >20% increase in tumor burden from baseline), death, or hospice entry. Real-world time to progression (rwTTP) was defined as time from index tx to first radiological progression.
Results:
A total of 115 patients were included; mean age was 65.1 years and 77% were male. At dx, 41% of patients were BCLC B, 14% were non-metastatic BCLC C, and 38% were BCLC A with lesion >5 cm, rapidly progressive disease, or contraindications to LRT. Tx initiation with TACE/TARE was common, either alone (n=59, 51%) or in combination with systemic tx (n=5, 4%). Among patients initiating systemic tx (n=46 ,40%), 30 received IO-IO (immuno-oncology) combinations, 12 received IO only, and 4 received a TKI only (tyrosine kinase inhibitor). Following index tx, 21 (18%) patients died receiving no subsequent tx and 27 (23%) were censored at data cutoff. Among those who received subsequent tx (n=67, 58%), there was heterogeneity in tx choice: TACE/TARE (n=32), systemic tx (n=16) other LRT (n=10), multimodal therapy (n=5), and transplant (n=4). We observed 60 progression events and 38 deaths corresponding to a median rwPFS and rwTTP of 7.9 (95% CI: 5.0, 13.3) months and 11.3 (95% CI: 6.7, 28.9) months, respectively.
Conclusions:
Our results showed high variability in management of uHCC eligible for LRT with TACE/TARE commonly utilized. Tx choice may be influenced by factors beyond staging criteria. Prognosis for uHCC eligible for LRT remains poor, and further research on adaptive, multimodal tx strategies is needed to inform tx guidelines and improve outcomes.