Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Figures & data

Table 1 Patient Baseline Characteristics of Triple Therapy and Monotherapy Groups Before and After PSM

Characteristics	Before PSM		P value	After PSM		P value
	Triple Therapy Group (n=41)	Monotherapy Group (n=63)		Triple Therapy Group (n=37)	Monotherapy Group (n=37)
Age, years, median (IQR)	52.0 (46.0–57.0)	54.0 (48.5–60.0)	0.224	53.0 (46.0–58.0)	52.0 (48.0–57.0)	0.961
Sex, n (%)
Male	35 (85.4)	56 (88.9)	0.820	32 (86.5)	31 (83.8)	>0.999
Female	6 (14.6)	7 (11.1)		5 (13.5)	6 (16.2)
HBV, n (%)
Absent	12 (29.3)	25 (39.7)	0.382	12 (32.4)	14 (37.8)	0.808
Present	29 (70.7)	38 (60.3)		25 (67.6)	23 (62.2)
Cirrhosis, n (%)
Absent	21 (51.2)	32 (50.8)	>0.999	20 (54.1)	17 (45.9)	0.642
Present	20 (48.8)	31 (49.2)		17 (45.9)	20 (54.1)
Portal hypertension, n (%)
Absent	33 (80.5)	44 (69.8)	0.326	29 (78.4)	26 (70.3)	0.595
Present	8 (19.5)	19 (30.2)		8 (21.6)	11 (29.7)
Ascites, n (%)
Absent	29 (70.7)	44 (69.9)	>0.999	25 (67.6)	27 (73.0)	0.799
Present	12 (29.3)	19 (30.2)		12 (32.4)	10 (27.0)
ALT, U/L, median (IQR)	38.0 (30.2–60.0)	46.0 (29.0–72.5)	0.299	39.0 (30.2–60.0)	37.0 (27.0–62.0)	0.585
;ALB, g/L, median (IQR)	36.2 (32.0–40.5)	34.9 (32.9–38.6)	0.32	36.2 (32.0–40.8)	36.1 (33.4–38.7)	0.897
TBIL, umol/L, median (IQR)	15.0 (11.4–26.0)	18.8 (13.9–29.3)	0.09	15.8 (12.8–26.7)	15.8 (12.7–22.2)	0.709
AFP, μg/L, n (%)
≤400	9 (22.0)	20 (31.7)	0.387	8 (21.6)	8 (21.6)	>0.999
>400	32 (78.0)	43 (68.3)		29 (78.4)	29 (78.4)
Child-Pugh class
A	32 (78.0)	40 (63.5)	0.176	28 (75.7)	29 (78.4)	>0.999
B	9 (22.0)	23 (36.5)		9 (24.3)	8 (21.6)
Tumor size, cm, median (IQR)	8.7 (6.6–11.6)	9.8 (6.6–12.7)	0.458	10.0 (6.7–12.0)	8.6 (5.3–12.7)	0.837
Tumor number, n (%)
Single	6 (14.6)	12 (19.0)	0.752	6 (16.2)	7 (18.9)	>0.999
Multiple	35 (85.4)	51 (81.0)		31 (83.8)	30 (81.1)
Extrahepatic metastasis, n (%)
Absent	31 (75.6)	43 (68.3)	0.557	27 (73.0)	25 (67.6)	0.799
Present	10 (24.4)	20 (31.7)		10 (27.0)	12 (32.4)
Portal vein tumor thrombus, n (%)
Absent	12 (29.3)	19 (30.2)	0.977	10 (27.0)	11 (29.7)	0.837
Vp-1	6 (14.6)	8 (12.7)		5 (13.5)	4 (10.8)
Vp-2	9 (22.0)	16 (25.4)		8 (21.6)	9 (24.3)
Vp-3	8 (19.5)	13 (20.6)		8 (21.6)	10 (27.0)
Vp-4	6 (14.6)	7 (11.1)		6 (16.2)	3 (8.1)
BCLC stage, n (%)			>0.999			0.794
B	11 (26.8)	18 (28.6)		9 (24.3)	11 (29.7)
C	30 (73.2)	45 (71.4)		28 (75.7)	26 (70.3)
Times of TACE	2 (2.0–3.0)	2 (2.0–3.0)	0.826	2 (2.0–3.0)	3 (2.0–3.0)	0.536

Abbreviations: PSM, propensity score matching; HBV, hepatitis B virus; ALT, alanine transaminase; ALB, albumin; TBIL, total bilirubin; AFP, alpha-fetoprotein; BCLC, Barcelona Clinic Liver Cancer; TACE, transarterial chemoembolization; IQR, interquartile range.

Figure 1 Flowchart of the study.

Abbreviations: HCC, hepatocellular carcinoma; BCLC, Barcelona Clinic Liver Cancer; TACE, transarterial chemoembolization.

Table 2 Univariate and Multivariate Analyses of Risk Factors for OS

Characteristics	Univariate Analysis			Multivariate Analysis
	HR	95% CI	P value	HR	95% CI	P value
Age (≥60 vs <60)	0.660	0.294–1.485	0.315
Sex (male vs female)	1.038	0.439–2.450	0.933
HBV (yes vs no)	0.928	0.506–1.704	0.810
Cirrhosis (yes vs no)	0.893	0.501–1.594	0.702
Portal hypertension (yes vs no)	0.662	0.328–1.336	0.250
Ascites (yes vs no)	0.960	0.497–1.856	0.904
AFP (>400 vs ≤400)	0.988	0.474–2.060	0.974
Child-Pugh class (B vs A)	1.362	0.689–2.692	0.374
Tumor size (≥5 vs <5)	2.188	0.926–5.174	0.074	2.326	0.970–5.578	0.059
Tumor number (≥2 vs 1)	1.913	0.755–4.849	0.172
Extrahepatic metastasis (yes vs no)	3.054	1.686–5.532	<0.001	2.062	1.069–3.975	0.031
PVTT (yes vs no)	3.289	1.527–7.085	0.002	1.135	0.142–9.052	0.905
BCLC stage (C vs B)	3.637	1.618–8.175	0.002	2.475	0.253–24.22	0.436
Treatment (triple therapy vs monotherapy)	0.527	0.292–0.952	0.034	0.449	0.240–0.840	0.012

Abbreviations: HR, hazard ratio; CI, confidence interval; HBV, hepatitis B virus; AFP, alpha-fetoprotein; PVTT, portal vein tumor thrombosis; BCLC, Barcelona Clinic Liver Cancer; OS, overall survival.

Figure 2 Kaplan–Meier survival curves for OS before PSM (A) and after PSM (B).

Abbreviations: OS, overall survival; PSM, propensity score matching.

Figure 3 Subgroup analysis of OS.

Abbreviations: HR, hazard ratio; CI, confidence interval; HBV, hepatitis B virus; AFP, alpha-fetoprotein; BCLC, Barcelona Clinic Liver Cancer; PVTT, portal vein tumor thrombosis; OS, overall survival. Bolded values indicate a statistical difference.

Table 3 Univariate and Multivariate Analyses of Risk Factors for PFS

Characteristics	Univariate Analysis			Multivariate Analysis
	HR	95% CI	P value	HR	95% CI	P value
Age (≥60 vs <60)	0.850	0.439–1.648	0.631
Sex (male vs female)	1.278	0.602–2.713	0.523
HBV (yes vs no)	0.890	0.516–1.533	0.674
Cirrhosis (yes vs no)	0.857	0.510–1.439	0.559
Portal hypertension (yes vs no)	0.608	0.328–1.336	0.109
Ascites (yes vs no)	0.943	0.529–1.679	0.841
AFP (>400 vs ≤400)	1.768	0.866–3.610	0.118
Child-Pugh class (B vs A)	1.140	0.613–2.121	0.680
Tumor size (≥5 vs <5)	1.417	0.714–2.812	0.319
Tumor number (≥2 vs 1)	1.348	0.661–2.748	0.411
Extrahepatic metastasis (yes vs no)	6.527	3.597–11.840	<0.001	6.858	3.471–13.55	<0.001
PVTT (yes vs no)	3.027	1.604–5.713	<0.001	2.502	0.324–19.33	0.379
BCLC stage (C vs B)	3.225	1.675–6.210	<0.001	0.976	0.112–8.506	0.982
Treatment (triple therapy vs monotherapy)	0.585	0.346–0.987	0.044	0.406	0.231–0.713	0.002

Abbreviations: HR, hazard ratio; CI, confidence interval; HBV, hepatitis B virus; AFP, alpha-fetoprotein; PVTT, portal vein tumor thrombosis; BCLC, Barcelona Clinic Liver Cancer; PFS, progression-free survival.

Figure 4 Kaplan–Meier survival curves for PFS before PSM (A) and after PSM (B).

Abbreviations: PFS, progression-free survival; PSM, propensity score matching.

Figure 5 Subgroup analysis of PFS.

Abbreviations: HR, hazard ratio; CI, confidence interval; HBV, hepatitis B virus; AFP, alpha-fetoprotein; BCLC, Barcelona Clinic Liver Cancer; PVTT, portal vein tumor thrombosis; PFS, progression-free survival. Bolded values indicate a statistical difference.

Table 4 Best Overall Response According to mRECIST

	Triple Therapy Group (n = 37)	Monotherapy Group (n = 37)	P value
Best Response
CR	3 (8.1%)	1 (2.7%)
PR	18 (48.6%)	11 (29.7%)
SD	10 (27.0%)	15 (40.5%)
ORR	21 (56.7%)	12 (32.4%)	0.035
DCR	31 (83.7%)	27 (72.9%)	0.259

Abbreviations: mRECIST, modified Response Evaluation Criteria in Solid Tumors; CR, complete response; PR, partial response; SD, stable disease; ORR, overall response rate; DCR, disease control rate.