Efficacy and Safety of TACE Combined with Lenvatinib and PD-(L)1 Inhibitor in the Treatment of Unresectable Hepatocellular Carcinoma: A Retrospective Study

Figures & data

Table 1 Baseline Characteristics of the Patients

Characteristic	TACE-L-P Group (n = 64)	TACE-L Group (n = 58)	P
Sex			0.852
Male	51 (79.7%)	47 (81.0%)
Female	13 (20.3%)	11 (19.0%)
Age (years)	61.4 ± 9.3	63.2 ± 8.5	0.252
ECOG PS			0.621
0	12 (20.7%)	11 (17.2%)
1	46 (79.3%)	53 (82.8%)
Child-Pugh class			0.782
A	38 (59.4%)	33 (56.9%)
B	26 (40.6%)	25 (43.1%)
BCLC			0.933
B	26 (40.6%)	24 (41.4%)
C	38 (59.5%)	34 (58.6%)
AFP			0.580
≤400ng/mL	31 (48.4%)	31 (53.4%)
>400ng/mL	33 (51.6%)	27 (46.6%)
Number of tumors			0.457
≤3	33 (51.6%)	26 (44.8%)
>3	31 (48.4%)	32 (55.2%)
Largest tumor size (mm)	78.8 ± 38.3	73.2 ± 35.8	0.339
PVTT			0.782
Yes	26 (40.6%)	25 (43.1%)
No	38 (59.4%)	33 (56.9%)
Hepatic vein invasion			0.572
Yes	16 (25.0%)	12 (20.7%)
No	48 (75.0%)	46 (79.3%)
Extrahepatic metastasis			0.611
Yes	13 (20.3%)	14 (24.1%)
No	51 (79.7%)	44 (75.9%)
TACE technique			0.319
C-TACE	47 (73.4%)	47 (81.0%)
D-TACE	17 (26.6%)	11 (19.0%)
Number of TACE	2.70 ±1.32	2.55 ± 1.08	0.491

Note: Data were presented as n (%) or mean ± standard deviation.

Abbreviations: TACE-L-P, transarterial chemoembolization combined with lenvatinib and PD-(L)1 inhibitor; TACE-L, transarterial chemoembolization combined with lenvatinib; ECOG PS, Eastern Cooperative Oncology Group Performance Status; AFP, a-fetoprotein; TACE, transarterial chemoembolization; C-TACE, conventional transarterial chemoembolization; D-TACE, drug-eluting bead transarterial chemoembolization.

Figure 1 Flow diagram showed selection criteria.

Abbreviations: uHCC, unresectable hepatocellular carcinoma; TACE-L-P, transarterial chemoembolization combined with lenvatinib and PD-(L)1 inhibitor; TACE-L, transarterial chemoembolization combined with lenvatinib.

Table 2 Tumor Response

Tumor Response	TACE-L-P	TACE-L	P
CR	11 (17.2%)	3 (5.2%)	0.022
PR	26 (40.6%)	21 (36.2%)
SD	23 (35.9%)	23 (39.6%)
PD	4 (6.3%)	11 (19%)
ORR (CR+PR)	37 (57.8%)	24 (41.4%)	0.047
DCR (CR+PR+SD)	60 (93.7%)	47 (81.0%)	0.013

Note: Data were presented as n (%) or mean ± standard deviation.

Abbreviations: TACE-L-P, transarterial chemoembolization combined with lenvatinib and PD-(L)1 inhibitor; TACE-L, transarterial chemoembolization combined with lenvatinib; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR (CR+PR), objective response rate; DCR (CR+PR+SD), disease control rate.

Table 3 Tumor Response of Different PD-(L)1 Inhibitor Groups

PD-(L)1 Inhibitor	CR	PR	SD	PD	P
Santolina	2 (16.7%)	6 (50.0%)	4 (33.3%)	0 (0%)	0.683
Tislelizumab	2 (28.6%)	1 (14.3%)	3 (42.8%)	1 (14.3%)
Tropaia	4 (23.5%)	6 (35.3%)	6 (35.3%)	1 (5.9%)
Camrelizumab	3 (10.7%)	14 (50.0%)	10 (35.7%)	1 (3.6%)

Notes: Data were presented as n (%) or mean ± standard deviation.

Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease.

Figure 2 Kaplan–Meier curves of progression-free survival.

Abbreviations: TACE-L-P, transarterial chemoembolization combined with lenvatinib and PD-(L)1inhibitor; TACE-L, transarterial chemoembolization combined with lenvatinib; HR, hazard ratio; CI, confidence interval.

Table 4 Univariate and Multivariate Analyses of Risk Factors for FPS

Factors	Univariate Analysis			Multivariate Analysis
	HR	95% CI	P	HR	95% CI	P
Sex
Male/Female	1.100	0.688–1.759	0.690
Age (years)
≤ 60 / >60	1.001	0.983–1.019	0.925
ECOG PS
0 / 1	1.426	0.885–2.299	0.145
Child-Pugh class
A / B	0.965	0.655–1.422	0.858
AFP (ng/mL)
≤400 / >400	1.257	0.856–1.846	0.242
Number of tumors
≤3 / >3	1.243	0.853–1.813	0.257
Largest tumor size (mm)
≤50 / >50	1.070	0.710–1.613	0.745
PVTT
Yes/No	1.599	1.095–2.336	0.017	2.033	1.363–3.033	0.001
Hepatic vein invasion
Yes/No	1.392	0.873–2.219	0.178
Extrahepatic metastasis
Yes/No	1.847	1.176–2.909	0.008	2.209	1.278–3.221	0.003
TACE technique
C-TACE / D-TACE	0.860	0.555–1.332	0.499
Treatment option
TACE-L-P / TACE-L	0.461	0.314–0.675	0.001	0.371	0.248–0.556	0.001

Abbreviations: HR, hazard ratio; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; AFP, alpha-fetoprotein; PVTT, portal vein tumor thrombus.

Table 5 Treatment-Related Adverse Events in Two Groups

Adverse Events	TACE-L-P (n = 64)		TACE-L (n = 58)		P
	Any Grade	Grade 3–4	Any Grade	Grade 3–4
Diarrhea	8 (12.5%)	1 (1.6%)	5 (8.6%)	1 (1.7%)	0.756
Hand-foot syndrome	11 (17.2%)	4 (6.3%)	7 (12.1%)	2 (3.4%)	0.808
Hypertension	17 (26.6%)	3 (4.7%)	13 (22.4%)	3 (5.2%)	0.764
Fatigue	23 (35.9%)	3 (4.7%)	19 (32.8%)	2 (3.4%)	0.824
Anorexia and nausea	25 (39.1%)	2 (3.2%)	21 (36.2%)	1 (1.7%)	0.678
Rash	19 (29.7%)	1 (1.6%)	20 (34.5%)	1 (1.7%)	0.972
Oral ulcer	15 (20.3%)	2 (3.1%)	13 (22.4%)	0 (0.0%)	0.492
Thyroid dysfunction	10 (15.6%)	4 (6.3%)	11 (19.0%)	2 (3.4%)	0.410
Hyperbilirubinemia	12 (18.8%)	3 (4.7%)	11 (19.0%)	3 (5.2%)	0.942
Thrombocytopenia	10 (15.6%)	2 (3.1%)	7 (12.1%)	1 (1.7%)	0.798

Note: Data were presented as n (%) or mean ± standard deviation.

Abbreviations: TACE-L-P, transarterial chemoembolization combined with lenvatinib and PD-(L)1 inhibitor; TACE-L, transarterial chemoembolization combined with lenvatinib.