ABSTRACT
Background:
The
role of transarterial chemoembolization (TACE) in the
treatment of advanced
hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the
efficacy and
safety of
immune checkpoint inhibitors (ICIs) plus anti-
vascular endothelial growth factor (anti-
VEGF) antibody/
tyrosine kinase inhibitors (TKIs) with or without TACE as first-line
treatment for advanced HCC.
Methods:
This nationwide, multicenter, retrospective
cohort study included advanced HCC
patients receiving either TACE with ICIs plus anti-
VEGF antibody/TKIs (TACE-ICI-
VEGF) or only ICIs plus anti-
VEGF antibody/TKIs (ICI-
VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse
probability of
treatment weighting (sIPTW) to minimize
biases. The primary outcome was overall
survival (OS).
Secondary outcomes included
progression-free survival (PFS), objective response rate (ORR), and
safety. The study is registered with ClinicalTrials.gov, NCT05332821.
Findings:
Among 1244
patients included in the
analysis, 802 (64.5%)
patients received TACE-ICI-
VEGF treatment, and 442 (35.5%)
patients received ICI-
VEGF treatment. The median follow-up
time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-
VEGF group exhibited a significantly improved median OS (22.6 months [95% CI 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted
hazard ratio [aHR] 0.63 [95% CI 0.53-0.75]). Median PFS was also longer in TACE-ICI-
VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (
RECIST) version 1.1. A higher ORR was observed in TACE-ICI-
VEGF group, by either
RECIST v1.1 or modified
RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178
patients (22.2%) in TACE-ICI-
VEGF group and 80
patients (18.1%) in ICI-
VEGF group.
Interpretation:
This
multicenter study supports the use of TACE combined with ICIs and anti-
VEGF antibody/TKIs as first-line
treatment for advanced HCC, demonstrating an acceptable
safety profile.
Funding:
National
Natural Science Foundation of
China, National Key
Research and Development Program of
China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of
Radiation Medicine of Jiangsu
Higher Education Institutions, and Nanjing
Life Health Science and
Technology Project.