Breaking through the transarterial chemoembolization resistance barrier: Reshaping the treatment path for advanced liver cancer with triple therapy

Table 1 Clinical trials for triple therapy in advanced liver cancer

Trial name	Therapeutic regimen	Sample size	Endpoint results	Limitation
EMERALD-1[17]	TACE + durvalumab ± bevacizumab	616	PFS benefit (HR = 0.77, triple therapy: 15.0 months, single-agent TACE: 8.2 months)	No OS difference, and excluded Child-Pugh B/C and VP4 grades
CHANCE001[18]	TACE + PD-L1 + MTT	826	OS benefit (HR = 0.63, triple therapy: 19.2 months, single-agent TACE: 15.7 months)	Retrospective design; no control of the dosage differences of targeted drugs
LEAP-012[19]	Lenvatinib + pembrolizumab → TACE	480	PFS benefit (HR = 0.66, triple therapy: 14.6 months, single-agent TACE: 10.0 months)	No OS benefit from reduction in sample size and insufficient follow-up time, deficiency in statistical power, and regional differences
TALENTACE[20]	TACE + atezolizumab + bevacizumab	342	PFS benefit (HR = 0.71, triple therapy: 11.3 months, single-agent TACE: 7.03 months)	The on-demand TACE design leads to heterogeneity in treatment frequency; no evolution of drug-resistant clones
Jiao et al[13]	TACE + PD-(L)1 + MTT	144	TACE resistance reduction, OS benefit (HR = 0.76, triple therapy: 20.8 months, single-agent TACE: 16.4 months)	Retrospective study with a small sample size

TACE: Transcatheter arterial chemoembolization; PD-L1: Programmed cell death-ligand 1; MTT: Multi-target receptor tyrosine kinase inhibitors; HR: Hazard ratio; VP4: Main portal vein tumor thrombus; OS: Overall survival; PFS: Progression-free-survival; PD-1: Programmed death 1.