Drug-eluting beads chemoembolization combined with programmed cell death 1 inhibitor and lenvatinib for large hepatocellular carcinoma

Table 1 Baseline characteristics of the patients

Characteristic	D-TACE-P-L group (n = 50)	C-TACE-P-L group (n = 54)	P value
Sex, n (%)			0.564
Male	42 (84.0)	43 (79.6)
Female	8 (16.0)	11 (20.4)
Age (years), mean ± SD	60.8 ± 9.2	62.2 ± 9.4	0.443
ECOG PS, n (%)			0.252
0	14 (28.0)	10 (18.5)
1	36 (72.0)	44 (81.5)
Child-Pugh class, n (%)			0.561
A	26 (52.0)	25 (46.3)
B	24 (48.0)	29 (53.7)
BCLC, n (%)			0.556
B	14 (28.0)	18 (33.3)
C	36 (72.0)	36 (66.7)
AFP, n (%)			0.727
≤ 400 ng/mL	23 (46.0)	23 (42.6)
> 400 ng/mL	27 (54.0)	31 (57.4)
Number of tumors, n (%)			0.392
≤ 3	31 (62)	29 (53.7)
> 3	19 (38)	25 (46.3)
Largest tumor size (mm), mean ± SD	96.3 ± 27.7	91.0 ± 36.7	0.324
PVTT, n (%)			0.873
No	23 (46.0)	24 (44.4)
Yes	27 (54.0)	30 (55.6)
Hepatic vein invasion, n (%)			0.656
No	38 (76.0)	43 (20.4)
Yes	12 (24.0)	11 (79.6)
Extrahepatic metastasis, n (%)			0.661
No	41 (82.0)	46 (85.2)
Yes	9 (18.0)	8 (14.8)
Number of TACE, mean ± SD	2.46 ± 1.0	2.56 ± 1.1	0.640

C-TACE-P-L: Conventional transarterial chemoembolization combined with lenvatinib plus programmed cell death 1 inhibitor; D-TACE-P-L: Drug-eluting beads transarterial chemoembolization combined with lenvatinib plus programmed cell death 1 inhibitor; ECOG PS: Eastern Cooperative Oncology Group Performance Status; BCLC: Barcelona Clinic Liver Cancer; AFP: Alpha-fetoprotein; PVTT: Portal vein tumor thrombus; TACE: Transarterial chemoembolization.

Table 2 Tumor response, n (%)

Tumor response	D-TACE-P-L	C-TACE-P-L	P value
CR	9 (18.0)	4 (7.4)	0.113
PR	24 (48.0)	20 (37.0)
SD	12 (24.0)	19 (35.2)
PD	5 (10.0)	11 (20.4)
ORR (CR + PR)	33 (66.0)	24 (44.4)	0.027
DCR (CR + PR + SD)	45 (90.0)	43 (81.0)	0.143

C-TACE-P-L: Conventional transarterial chemoembolization combined with lenvatinib plus programmed cell death 1 inhibitor; D-TACE-P-L: Drug-eluting beads transarterial chemoembolization combined with lenvatinib plus programmed cell death 1 inhibitor; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; ORR: Objective response rate; DCR: Disease control rate.

Table 3 Tumor response of different programmed cell death 1 inhibitor groups, n (%)

PD-1 inhibitor	CR	PR	SD	PD	P value
Tislelizumab	2 (14.3)	5 (35.7)	4 (28.6)	3 (24.1)	0.927
Sintilimab	1 (5.9)	10 (58.8)	5 (29.4)	1 (5.9)
Camrelizumab	6 (13.3)	17 (37.8)	14 (31.1)	8 (17.8)
Toripalimab	4 (14.3)	12 (42.9)	8 (28.5)	4 (14.3)

PD-1: Programmed cell death 1; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease.

Table 4 Univariate and multivariate analyses of risk factors for progression-free survival

Factors	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Sex
Male/female	1.145	0.692-49	0.599
Age (years)	1.007	0.987-1.027	0.495
ECOG PS
0/1	1.246	0.781-1.988	0.357
Child-Pugh class
A/B	1.301	0.881-1.921	0.185
AFP (ng/mL)
≤ 400/> 400	1.215	0.821-1.798	0.329
Number of tumors
≤ 3/> 3	1.276	0.857-1.900	0.229
Largest tumor size (mm)	1.006	0.998-1.013	0.139
PVTT
No/yes	1.590	1.073-2.358	0.021	1.670	1.120-2.491	0.012
Hepatic vein invasion
No/yes	1.621	1.012-2.596	0.044	1.807	1.105-2.956	0.018
Extrahepatic metastasis
No/yes	1.778	1.038-3.044	0.036	1.554	0.900-2.686	0.114
Treatment option
D-TACE-P-L/C-TACE-P-L	1.422	0.961-2.104	0.078	1.536	1.028-2.293	0.036

C-TACE-P-L: Conventional transarterial chemoembolization combined with lenvatinib plus programmed cell death 1 inhibitor; D-TACE-P-L: Drug-eluting beads transarterial chemoembolization combined with lenvatinib plus programmed cell death 1 inhibitor; ECOG PS: Eastern Cooperative Oncology Group Performance Status; AFP: Alpha-fetoprotein; PVTT: Portal vein tumor thrombus; HR: Hazard ratio; CI: Confidence interval.

Table 5 Treatment-related adverse events in the two groups, n (%)

Adverse events	D-TACE-P-L (n = 50)		C-TACE-P-L (n = 54)		P value
	Any grade	Grade 3	Any grade	Grade 3
Diarrhea	9 (18.0)	2 (4.0)	7 (13.0)	1 (1.8)	0.717
Hand-foot syndrome	12 (24.0)	2 (4.0)	15 (27.8)	2 (3.7)	0.882
Hypertension	13 (26.0)	1 (2.0)	14 (26.0)	0 (0.0)	0.572
Fatigue	24 (48.0)	4 (8.0)	20 (37.0)	3 (5.6)	0.522
Anorexia and nausea	26 (52.0)	4 (8.0)	30 (55.6)	5 (9.3)	0.928
Rash	19 (38.0)	1 (2.0)	25 (46.3)	3 (5.6)	0.518
Thyroid dysfunction	6 (12.0)	0 (0.0)	10 (18.5)	1 (1.8)	0.485
Hyperbilirubinemia	11 (22.0)	2 (4.0)	9 (16.7)	1 (1.8)	0.738
Fever	46 (92.0)	6 (12.0)	48 (89.9)	3 (5.6)	0.462
Abdominal pain	34 (68.0)	6 (12.0)	33 (61.1)	2 (3.7)	0.336

C-TACE-P-L: Conventional transarterial chemoembolization combined with lenvatinib plus programmed cell death 1 inhibitor; D-TACE-P-L: Drug-eluting beads transarterial chemoembolization combined with lenvatinib plus programmed cell death 1 inhibitor.