Safety and Efficacy of Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma: A Single Center Experience

Figures & data

Table 1 Baseline Characteristics of 49 Patients

Characteristics	Patients (N = 49)	Characteristics	Patients (N = 49)	Characteristics	Patients (N = 49)
Height (cm), Mean (SD)	167.4 (5.4)	Tumor location, n (%)		Tumor number, n (%)
Weight (kg), Mean (SD)	64.1 (9.6)	Left lobe	8 (16.3)	<3	23 (46.9)
Age (Year), n (%)		Right lobe	22 (44.9)	≥3	26 (53.1)
<65	38 (77.6)	Bilateral lobes	19 (38.8)	Liver cirrhosis, n (%)
≥65	11 (22.4)	Liver capsule, n (%)		YES	28 (57.1)
Sex, n (%)		Complete	24 (49.0)	NO	21 (42.9)
Male	46 (93.9)	Infiltrated	25 (51.0)	Ascites, n (%)
Female	3 (6.1)	Tumor size (cm), n (%)		YES	18 (36.7)
ECOG PS, n (%)		<10 cm	18 (36.7)	NO	31 (63.3)
0	33 (67.3)	≥10cm	31 (63.3)	AFP (ng/mL) n (%)
1	16 (32.7)	Extrahepatic metastasis, n (%)		<400	21 (42.9)
Child-Pugh classification, n (%)		YES	6 (12.2)	≥400	28 (57.1)
A	40 (81.6)	NO	43 (87.8)	AST (U/L), n (%)
B	9 (18.4)	HVTT, n (%)		<40	12 (24.5)
CNLC stage, n (%)		YES	14 (28.6)	≥40	37 (75.5)
Ib	5 (10.2)	NO	35 (71.4)	ALT (U/L), n (%)
IIa	5 (10.2)	IVCTT, n (%)		<50	24 (49)
IIb	9 (18.4)	YES	4 (8.2)	≥50	25 (51)
IIIa	24 (49.0)	NO	45 (91.8)	Albumin (g/L), Mean (SD)	39.8 (6.0)
IIIb	6 (12.2)	HAPFS, n (%)		Total bilirubin (µmol/L), Mean (P25, P75)	14.4 (11.5, 24.8)
BCLC stage, n (%)		YES	5 (10.2)	Platelet (109/L), Mean (SD)	234.8 (95.2)
A	5 (10.2)	NO	44 (89.8)	AP (mAU/mL), M (P25, P75)	7990.0 (449.5, 75,000.0)
B	14 (28.6)	Hepatitis B, n (%)		PT (s), Mean (SD)	11.9 (1.0)
C	30 (61.2)	YES	41 (83.7)	PVTT, n (%)
		NO	8 (16.3)	YES	27 (55.1)
				NO	22 (44.9)

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group Performance Status; CNLC, China Liver Cancer Staging; BCLC, Barcelona Clinic Liver Cancer; PVTT, portal vein tumor thrombus; HVTT, hepatic vein tumor thrombus; IVCTT, inferior vena cava tumor thrombus; HAPFS, hepatic arterioportal fistula; AFP, Alpha-fetoprotein; AST, Aspartate aminotransferase; ALT, Alanine aminotransferase; AP, abnormal prothrombin; PT, prothrombin time.

Table 2 Radiological Response According to mRECIST and RECISTv1.1

	MRECIST (N = 42)	RECIST v1.1 (N = 42)
CR	2 (4.8%)	0
PR	22 (52.4%)	6 (14.3%)
SD	15 (35.7%)	31 (73.8%)
PD	3 (7.1%)	5 (11.9%)
ORR	24 (57.1%)	6 (14.3%)
DCR	39 (92.9%)	37 (88.1%)

Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate.

Table 3 Radiological Response in the Subgroups According to mRECIST

	BCLC Stage A (N = 5)	BCLC Stage B (N = 14)	BCLC Stage C (N = 30)
CR	0	1 (7.14%)	1 (3.3%)
PR	2 (40%)	8 (57.14%)	12 (40%)
SD	2 (40%)	3 (21.43%)	10 (33.3%)
PD	0	0	3 (10%)
NE	1 (20%)	2 (14.29%)	4 (13.3%)

Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; NE, not evaluable.

Table 4 Radiological Response in the Subgroups (d-TACE and c-TACE) According to mRECIST

	d-TACE (N = 18)	c-TACE (N = 24)	χ^2 test
			χ^2 value	P value
CR	1 (5.6%)	1 (4.2%)	1.680	P = 0.708
PR	10 (55.6%)	12 (50%)
SD	5 (27.8%)	10 (41.7%)
PD	2 (11.1%)	1 (4.2%)
ORR	11 (61.1%)	13 (54.2%)	0.203	P = 0.653
DCR	16 (88.9%)	23 (95.8%)	0.067	P = 0.795

Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate.

Table 5 Baseline Characteristics in 17 Patients for Surgical Resection

Characteristics	Patients (N = 49)	Characteristics	Patients (N = 49)	Characteristics	Patients (N = 49)
Height (cm), Mean (SD)	168.6 (5.4)	Tumor location, n (%)		Tumor number, n (%)
Weight (kg), Mean (SD)	62.7 (10.6)	Left lobe	4 (23.5)	<3	8 (47.1)
Age (Year), n (%)		Right lobe	8 (47.1)	≥3	9 (52.9)
<65	12 (70.6)	Bilateral lobes	5 (29.4)	Liver cirrhosis, n (%)
≥65	5 (29.4)	Liver capsule, n (%)		YES	7 (41.2)
Sex, n (%)		Complete	9 (52.9)	NO	10 (58.8)
Male	17 (100)	Infiltrated	8 (47.1)	Ascites, n (%)
Female	0 (0)	Tumor size (cm), n (%)		YES	2 (11.8)
ECOG PS, n (%)		<10 cm	6 (35.3)	NO	15 (88.2)
0	9 (52.9)	≥10cm	11 (64.7)	AFP (ng/mL) n (%)
1	8 (47.1)	Extrahepatic metastasis, n (%)		<400	7 (41.2)
Child-Pugh classification, n (%)		YES	2 (11.8)	≥400	10 (58.8)
A	16 (94.1)	NO	15 (88.2)	AST (U/L), n (%)
B	1 (5.9)	HVTT, n (%)		<40	5 (29.4)
CNLC stage, n (%)		YES	5 (29.4)	≥40	12 (70.6)
Ib	1 (5.9)	NO	12 (70.6)	ALT (U/L), n (%)
IIa	3 (17.6)	IVCTT, n (%)		<50	8 (47.1)
IIb	4 (23.5)	YES	2 (11.8)	≥50	9 (52.9)
IIIa	7 (41.2)	NO	15 (88.2)	Albumin (g/L), Mean (SD)	42.1 (4.8)
IIIb	2 (11.8)	HAPFS, n (%)		Total bilirubin (µmol/L), Mean (P25, P75)	17.5 (8.4)
BCLC stage, n (%)		YES	1 (5.9)	Platelet (109/L), Mean (SD)	244.4 (95.8)
A	1 (5.9)	NO	16 (94.1)	AP (mAU/mL), M (P25, P75)	5367 (1956, 60,031.5)
B	7 (41.1)	Hepatitis B, n (%)		PT (s), Mean (SD)	11.5 (0.9)
C	9 (52.9)	YES	12 (70.6)	PVTT, n (%)
		NO	5 (29.4)	YES	9 (52.9)
				NO	8 (47.1)

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group Performance Status; CNLC, China Liver Cancer Staging; BCLC, Barcelona Clinic Liver Cancer; PVTT, portal vein tumor thrombus; HVTT, hepatic vein tumor thrombus; IVCTT, inferior vena cava tumor thrombus; HAPFS, hepatic arterioportal fistula; AFP, Alpha-fetoprotein; AST, Aspartate aminotransferase; ALT, Alanine aminotransferase; AP, abnormal prothrombin; PT, prothrombin time.

Table 6 Adverse Events

Event	Any Grade (n = 48)	Grade 3 or 4 (n = 18)
Hypertension	6 (12.2%)	1 (2.0%)
Aspartate aminotransferase increase	38 (77.6%)	15 (30.6%)
Alanine aminotransferase increase	23 (46.9%)	5 (10.2%)
Blood bilirubin increase	1 (2.0%)	0
Platelet count decrease	22 (44.9%)	4 (8.2%)
Creatinine increase	3 (6.1%)	0
Fatigue	14 (28.6%)	0
Proteinuria	26 (53.1%)	0
Pruritus	3 (6.1%)	0
Diarrhea	2 (4.1%)	0
Decreased appetite	11 (22.4%)	0
Pyrexia	8 (16.3%)	0
Constipation	4 (8.2%)	0
Rash	2 (4.1%)	0
Abdominal pain	36 (73.5%)	0
Nausea	14 (28.6%)	1 (2.0%)
Hand–foot skin reaction	1 (2.0%)	0
Epistaxis	4 (8.2%)	0
Alopecia	6 (12.2%)	0
Hypothyroidism	11 (22.4%)	0
Hemorrhage from gastric varices	1 (2.0%)	1 (2.0%)
Myosalgia	1 (2.0%)	0