Present and prospect of transarterial chemoembolization combined with tyrosine kinase inhibitor and PD-1 inhibitor for unresectable hepatocellular carcinoma

Table 1 Characteristics of clinical trials evaluating the transarterial chemoembolization combined with multi-targeted tyrosine kinase inhibitor and programmed cell death protein-1 inhibitor for unresectable hepatocellular carcinoma

Ref.	Study design	Sample size	Hepatocellular carcinoma stage	TACE	TKI	PD-1	Administration sequence	Outcomes
Qin et al[23], 2022	Retrospective, double-arm	25 (TACE + TKI + PD-1) vs 41 (TACE + PD-1)	Advanced	Pirarubicin, epirubicin, loplatin, raltitrexed	Sorafenib	Sintilimab or camrelizumab	TKI+PD-1 after initial TACE, TKI before and after each subsequent TACE vs PD-1 after initial TACE	OS: 21.63 months vs 16.43 months, P = 0.103; PFS: 7.63 months vs 2.9 months, P = 0.034; ORR: 59.09% vs 50%, P = 0.761; DCR: 95.45% vs 72.72%, P = 0.095
Chen et al[24], 2022	Retrospective, double-arm	70 (TACE + TKI + PD-1) vs 72 (TACE + TKI)	Unresectable	Pharmorubicin	Lenvatinib	Pembrolizumab	TKI+PD-1 before initial TACE vs TKI before initial TACE	OS: 18.1 months vs 14.1 months, P = 0.004; PFS: 9.2 months vs 5.5 months, P = 0.006
Wang et al[25], 2023	Retrospective, double-arm	46 (TACE + TKI + PD-1) vs 59 (TKI+PD-1)	Unresectable	Epirubicin, raltitrexed, oxaliplatin	Lenvatinib	Pembrolizumab, camrelizumab, or sintilimab	TKI after initial TACE, then PD-1 within 7 days of initial MKI vs TKI+PD-1	OS: 20.5 months vs 12.6 months, P = 0.015; PFS: 10.2 months vs 7.4 months, P = 0.035; ORR: 54.3% vs 25.4%, P = 0.002; DCR: 82.6% vs 64.4%, P = 0.038
Ma et al[26], 2024	Retrospective, single-arm	102 (TACE + TKI + PD-1)	Unresectable	Epirubicin, oxaliplatin, 5-fluorouracil, calcium folinate	Lenvatinib	Sintilimab, nivolumab, camrelizumab, pembrolizumab, toripalimab	TKI+PD-1 after initial TACE	OS: 26.43 months; PFS: 10.07 months; ORR: 61.76%; DCR: 81.37%
Dong et al[11], 2023	Retrospective, double-arm	228 (TACE + MKI + PD-1) vs 228 (TACE)	Unresectable	NA	Sorafenib, lenvatinib, donafenib, regorafenib, apatinib, anlotinib, bevacizumab	Atezolizumab, pembrolizumab, nivolumab, camrelizumab, sintilimab, tislelizumab, toripalimab	PD-1 at least 3 days before or after TACE, TKI within two weeks before or after TACE	OS: 19.2 months vs 15.7 months, P = 0.037; PFS: 9.5 months vs 8.0 months, P = 0.015; ORR: 60.1% vs 32.0%, P < 0.001

DCR: Disease control rate; TACE: Transarterial chemoembolization; TKI: Tyrosine kinase inhibitor; PD-1: Programmed cell death protein-1; MKI: Multikinase inhibitors; OS: Overall survival; ORR: Objective response rate; PFS: Progression-free survival.