Clinical benefits of transarterial chemoembolization combined with tyrosine kinase and immune checkpoint inhibitors for unresectable hepatocellular carcinoma

Table 1 Baseline characteristics of includes studies and patients

Ref.	Country	Subjects	Study design	Treatment regimen	Sample size	Age (yr)	Male (%)	Positive of HBV (%)	AFP < 400 ng/mL (%)	Child-Pugh A (%)	BCLC stage A/B/C	EHM (%)	PVTT (%)
Yuan et al[18], 2024	China	Patients with unresectable HCC	Retrospective	TACE + TKIs + ICIs	139	59 (50, 67)	121 (87.05)	115 (82.73)	103 (74.10)	119 (85.61)	0/99/40	23 (16.55)	31 (22.3)
Sun et al[19], 2024	China	Patients with advanced HCC	Retrospective	TACE + lenvatinib + sintilimab	40	55 ± 9	34 (85.0)	30 (75.0)	26 (65.0)	34 (85.0)	0/0/40	14 (35.0)	29 (72.5)
Sheng et al[20], 2024	China	Patients with unresectable HCC	Retrospective	TACE + lenvatinib + PD-1 inhibitor	113	64.48 ± 10.83	95 (84.1)	72 (63.7)	90 (79.6)	88 (77.9)	0/54/59	15 (13.3)	29 (25.7)
Cai et al[17], 2024	China	Patients with advanced HCC	Retrospective	TACE + lenvatinib + sintilimab	30	49.4 ± 9.9	26 (86.7)	25 (83.3)	NR	29 (96.7)	NR	13 (43.3)	NR
Gao et al[21], 2023	China	Patients with advanced HCC	Retrospective	TACE + TKIs + ICIs	41	52 (46, 57)	35 (85.4)	29 (70.7)	9 (22.0)	32 (78.0)	0/11/30	10 (24.4)	29 (70.7)
Li et al[22], 2023	China	Patients with advanced HCC	Prospective	TACE + TKIs + camrelizumab	87	56 (34, 75)	81 (93.1)	75 (86.2)	51 (58.6)	51 (58.6)	NR/NR/69	43 (49.4)	65 (74.7)
Hu et al[44], 2023	China	Patients with unresectable HCC	Retrospective	TACE + TKIs + ICIs	98	52 (42, 62)	87 (88.8)	85 (86.7)	NR	75 (76.5)	0/12/86	49 (50.0)	14 (14.3)
Zhang et al[23], 2024	China	Patients with unresectable HCC	Retrospective	TACE + TKIs + ICIs	54	≤ 60: 38 (72.5); > 60: 16 (27.5)	46 (85.0)	53 (98.1)	26 (48.1)	54 (100)	0/23/31	19 (35.2)	NR
Wu et al[24], 2024	China	Patients with unresectable HCC	Prospective	TACE + lenvatinib + camrelizumab	55	54 (46, 62)	45 (81.8)	27 (49.1)	23 (41.8)	55 (100)	0//12/43	10 (18.2)	37 (67.3)
Gao et al[25], 2023	China	Patients with TACE-refractory HCC	Retrospective	TACE + lenvatinib + PD-1 inhibitor	57	57.5 ± 9.4	45 (78.9)	43 (75.4)	NR	34 (59.6)	0/17/40	24 (42.1)	NR
Lu et al[26], 2023	China	Patients with unresectable HCC	Retrospective	TACE + donafenib + toripalimab	81	51.9±12.4	65 (80.2)	54(66.7)	NR	46 (56.8)	0/22/59	NR	NR
Pan et al[27], 2023	China	Patients with unresectable HCC	Retrospective	TACE + TKIs + ICIs	49	< 65: 38 (77.6); ≥ 65: 11 (22.4)	46 (93.9)	41 (83.7)	21 (42.9)	40 (81.6)	5/14/30	6 (12.2)	27 (55.1)
Wu et al[28], 2023	China	Patients with BCLC-defined stage C HCC	Retrospective	TACE + lenvatinib + camrelizumab	57	53.18 ± 9.25	49 (86.0)	44 (77.2)	25 (43.9)	52 (91.2)	0/0/57	23 (40.4)	NR
Wang et al[29], 2023	China	Patients with unresectable HCC	Retrospective	TACE + lenvatinib + PD-1 inhibitor	45	54 (18, 79)	42 (93.33)	42 (93.33)	13 (28.89)	NR	NR	18 (40.0)	20 (44.44)
Xin et al[30], 2023	China	Patients with unresectable HCC	Retrospective	TACE + lenvatinib + PD-1 inhibitor	60	57.5 (26, 76)	54 (90.0)	56 (93.4)	32 (53.3)	NR	0/21/39	18 (30.0)	28 (46.7)
Wang et al[31], 2023	China	Patients with unresectable HCC	Retrospective	TACE + lenvatinib + PD-1 inhibitor	46	55.54 ± 11.92	41 (89.1)	42 (91.3)	18 (39.1)	38 (82.6)	0/8/38	24 (52.2)	NR
Sun et al[32], 2023	China	Patients with advanced HCC	Retrospective	TACE + TKIs + camrelizumab	70	53.8 ± 10.4	58 (82.9)	54 (77.1)	30 (42.9)	57 (81.4)	NR	NR	NR
Ju et al[33], 2021	China	Patients with unresectable HCC	Retrospective	TACE + apatinib + camrelizumab	56	52 (26, 75)	46 (82.1)	48 (85.7)	NR	43 (76.8)	0/13/43	NR	NR
Cai et al[34], 2022	China	Patients with advanced HCC	Retrospective	TACE + lenvatinib + PD-1 inhibitor	41	51.9 ± 10.3	37 (90.2)	35 (85.4)	20 (48.8)	37 (90.2)	NR	17 (41.5)	NR
Li et al[35], 2022	China	Patients with unresectable HCC	Retrospective	TACE + lenvatinib + PD-1 inhibitor	114	53 (24, 79)	102 (89.5)	102 (89.5)	NR	111 (97.4)	3/42/69	23 (20.2)	NR
Teng et al[36], 2022	China	Patients with unresectable HCC	Retrospective	TACE + lenvatinib + PD-1 inhibitor	53	56.9 (37, 75)	45 (84.9)	45 (84.9)	35 (66.0)	34 (64.2)	0/23/30	42 (79.2)	NR
Qu et al[37], 2022	China	Patients with unresectable HCC	Retrospective	TACE + lenvatinib + PD-1 inhibitor	56	51 (24, 82)	51 (91.1)	43 (76.8)	34 (60.7)	53 (94.6)	0/17/39	29 (51.8)	NR
Yang et al[38], 2022	China	Patients with unresectable HCC	Retrospective	TACE + TKIs + ICIs	53	59 ± 10.6	45 (85.0)	47 (89.0)	34 (64.0)	34 (64.0)	2/29/22	NR	NR
Yang et al[39], 2021	China	Patients with unresectable HCC	Retrospective	TACE + TKIs + ICIs	31	57.5 ± 9.4	25 (80.6)	26 (83.9)	23 (74.2)	27 (87.1)	2/18/11	NR	NR
Liu et al[45], 2021	China	Patients with advanced HCC	Retrospective	TACE + lenvatinib + camrelizumab	22	57.7 ± 9.9	17 (77.3)	15 (68.2)	7 (31.2)	16 (72.7)	0/12/10	8 (36.4)	11 (50.0)
Wu et al[40], 2021	China	Patients with unresectable HCC	Retrospective	TACE + lenvatinib + Anti-PD-1 antibodies	62	57 (23, 75)	56 (90.3)	57 (91.9)	30 (48.4)	62 (100.0)	6/21/35	6 (9.7)	15 (24.2)
Cao et al[41], 2021	China	Patients with unresectable HCC	Retrospective	TACE + lenvatinib + sintilimab	52	≤ 65: 40 (76.9); > 65: 12 (23.1)	45 (86.4)	47 (90.4)	34 (65.4)	46 (88.5)	0/13/39	21 (40.4)	NR
Zheng et al[42], 2020	China	Patients with advanced TACE-refractory HCC	Retrospective	TACE + sorafenib + ICIs	22	< 55: 10 (45.45); ≥ 55: 12 (54.55)	19 (86.36)	17 (77.27)	7(31.82)	13 (59.03)	0/11/11	7(31.82)	7(31.82
Chen et al[43], 2022	China	Patients with unresectable HCC	Retrospective	TACE + lenvatinib + pembrolizumab	70	58 (36, 69)	37 (52.9)	38 (54.3)	25 (35.7)	70 (100.0)	0/47/23	NR	NR

HCC: Hepatocellular carcinoma; TACE: Transarterial chemoembolization; TKI: Tyrosine kinase inhibitor; ICI: Immune checkpoint inhibitor; HBV: Hepatitis B virus; AFP: α-fetoprotein; BCLC: Barcelona Clinic Liver Cancer; EHM: Extrahepatic metastasis; PVTT: Portal vein tumor thrombosis.

Table 2 Ongoing clinical trials for triple therapy

Combination regimen	Comparator	Cancer stage	NCT number	Phase	Primary endpoint
TACE + lenvatinib + sintilimab/camrelizumab	None	Advanced unresectable HCC	NCT04997850	Ⅰ/Ⅱ	Conversion resection rate
TACE + lenvatinib + ICIs	None	Intermediate/advanced HCC	NCT04974281	Ⅰ	Conversion resection rate
TACE + donafenib + ICIs	None	Advanced HCC	NCT05262959	Ⅱ	PFS
TACE + sorafenib + ICIs	None	Intermediate/advanced HCC	NCT04518852	Ⅱ	ORR, OS
TACE + sorafenib + tilelizumab	None	Advanced HCC	NCT04992143	Ⅱ	1-yr survival rate
TACE + lenvatinib + tislelizumab	None	Advanced unresectable HCC	NCT05131698	Ⅰ	ORR
TACE + sorafenib + tilelizumab	None	Advanced HCC	NCT04599777	Ⅱ	OS
TACE + lenvatinib + durvalumab + tremelimumab	TACE	Locoregional HCC not amenable to curative therapy	NCT05301842	Ⅲ	PFS
TACE + lenvatinib + pembrolizumab	TACE	Incurable/Non-metastatic HCC	NCT04246177	Ⅲ	PFS, OS

PFS: Progression-free survival; OS: Overall survival; ORR: Objective response rate; HCC: Hepatocellular carcinoma; TACE: Transarterial chemoembolization; ICI: Immune checkpoint inhibitor.