Efficacy and Safety of HepaSphere Drug-Eluting Bead Transarterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy as the Second-Line Treatment in Advanced Hepatocellular Carcinoma

Figures & data

Figure 1 Protocol of this study.

Abbreviations: HCC, Hepatocellular carcinoma; HAIC, hepatic arterial infusion chemotherapy; PSM, propensity score matching; OS, overall survival; PFS, progression-free survival; ORR, objective response rate; AE, adverse event.

Table 1 Baseline Characteristics of Patients with Advanced HCC (Before PSM)

Characteristic	Hepa-HAIC (n=74)	HAIC (n=93)	p
Age(y)			0.691
≤65	46 (62.2)	55 (59.1)
>65	28 (37.8)	38 (40.9)
Gender			0.309
Male	64 (86.5)	85 (91.4)
Female	10 (13.5)	8 (8.6)
ECOG			0.703
0	38 (51.4)	45 (48.4)
1	36 (48.6)	48 (51.6)
Hepatitis			0.256
No	6 (8.1)	8 (8.6)
HBV	60 (81.1)	82 (88.2)
HCV	4 (5.4)	4 (4.3)
Both	4 (5.4)	1 (1.1)
Child-Pugh			0.108
A	71 (96.0)	83 (89.2)
B	3 (4.0)	10 (10.8)
AFP (ng/mL)			0.83
≤400	51 (68.9)	68 (73.1)
>400	23 (31.1)	25 (26.9)
Tumor number			0.887
Single	15 (20.3)	17 (18.3)
Multiple	59 (79.7)	76 (81.7)
Tumor size (cm)			0.405
≤5	35 (47.3)	38 (40.9)
>5	39 (52.7)	55 (59.1)
Vein invasion			<0.001
Yes	27 (63.5)	61 (65.6)
No	47 (36.5)	32 (34.4)
Previous treatment			0.736
No	3 (4.0)	6 (6.5)
Yes	71 (96.0)	87 (93.5)
Extrahepatic metastasis			0.071
No	39 (52.7)	36 (38.7)
Yes	35 (47.3)	57 (61.3)

Abbreviations: AFP, alpha fetoprotein; ECOG PS, Eastern Cooperative Oncology Group.

Table 2 Baseline Characteristics of Patients with Advanced HCC (After PSM)

Characteristic	Hepa-HAIC (n=48)	HAIC (n=48)	p
Age			1.00
≤65	31 (64.6)	31 (64.6)
>65	17 (35.4)	17 (35.4)
Gender			0.486
Male	42 (87.5)	45 (93.8)
Female	6 (12.5)	3 (6.2)
ECOG PS			1.000
0	23 (47.9)	23 (47.9)
1	25 (52.1)	25 (52.1)
Hepatitis			0.416
No	3 (6.3)	5 (10.4)
HBV	41 (85.4)	42 (87.5)
HCV	2 (4.2)	1 (2.1)
Both	2 (4.2)	0 (0)
Child-Pugh			0.317
A	45 (93.8)	41 (85.4)
B	3 (6.2)	7 (14.6)
AFP (ng/mL)			0.181
≤400	41 (85.4)	45 (93.8)
>400	7 (15.6)	3 (6.3)
Tumor number			0.537
Single	5 (10.4)	7 (14.6)
Multiple	43 (89.6)	41 (85.4)
Tumor size (cm)			0.297
≤5	22 (45.8)	16 (33.3)
>5	26 (33.3)	32 (66.7)
Vein invasion			0.404
Yes	27 (56.3)	31 (64.6)
No	21 (43.7)	17 (35.4)
Previous treatment			1.0
Yes	46 (95.8)	45 (93.8)
No	2(4.2)	3 (6.2)
Extrahepatic metastasis			0.157
No	15 (31.3)	9 (18.7)
Yes	33 (68.8)	39 (81.3)

Abbreviations: AFP, alpha fetoprotein; ECOG PS, Eastern Cooperative Oncology Group.

Table 3 Tumor Response

Response (By mRECIST)	Matched Cohort (n=96)
	Hepa-HAIC (n=48)	TACE (n=48)	P value
Complete response	4 (8.3)	2 (4.2)	<0.001
Partial response	32 (66.7)	16 (33.3)	<0.001
Stable disease	9 (18.8)	21 (43.8)	0.012
Objective response rate	36 (75.0)	18 (37.5)	<0.001
Disease control rate	45 (93.8)	39 (81.3)	0.002

Table 4 Univariate and Multivariate Analysis of Risk Factors for OS (After PSM)

Characteristic	Overall Survival
	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	P	HR (95% CI)	P
Treatment	0.560 (0.330–0.950)	0.027	0.560 (0.332–0.946)	0.030
Age, year (≤/>65)	1.300 (0.760–2.210)	0.344
Gender (male/female)	1.160 (0.490–2.730)	0.734
ECOG PS (0/1)	0.972 (0.561–1.685)	0.920
Hepatitis (no/yes)	0.602 (0.289–1.255)	0.172	0.691 (0.321–1.491)	0.347
Child-Pugh (A/B)	1.450 (0.860–2.430)	0.164	0.905 (0.349–2.349)	0.838
AFP, ng/mL (≤/>400)	1.048 (0.627–1.749)	0.859
Tumor number (single/multiple)	1.399 (0.695–2.818)	0.347
Tumor size, cm (≤/>5)	1.121 (0.658–1.912)	0.673
Vein invasion (yes/no)	1.415 (0.823–2.433)	0.202
Previous treatment (no/yes)	0.927 (0.549–1.566)	0.777
Extrahepatic metastasis (yes/no)	1.167 (0.649–2.099)	0.603

Abbreviations: HR, hazard ratio; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group; AFP, alpha fetoprotein.

Table 5 Univariate and Multivariate Analysis of Risk Factors for PFS (After PSM)

	Progression-free Survival
Characteristic	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	P	HR (95% CI)	P
Treatment	0.633 (0.409–0.982)	0.035	0.580 (0.372–0.906)	0.017
Age, year (≤/>65)	1.699 (1.076–2.684)	0.026	1.859 (1.168–2.959)	0.009
Gender (male/female)	1.524 (0.753–3.086)	0.241
ECOG PS (0/1)	1.524 (0.753–3.086)	0.265
Hepatitis (no/yes)	0.856 (0.457–1.603)	0.626
Child-Pugh (A/B)	0.664 (0.268–1.647)	0.377
AFP, ng/mL (≤/>400)	1.281 (0.826–1.985)	0.268
Tumor number (single/multiple)	1.402 (0.711–2.765)	0.330
Tumor size, (≤/>5 cm)	0.942 (0.597–1.486)	0.798
Vein invasion (yes/no)	1.310 (0.831–2.067)	0.245
Previous treatment	0.942 (0.596–1.488)	0.798
Extrahepatic metastasis (yes/no)	1.106 (0.670–1.828)	0.693

Abbreviations: HR, hazard ratio; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group; AFP, alpha fetoprotein.

Figure 2 Overall survival curves (A) and progression-free survival curves (B) for patients who received Hepa-HAIC and HAIC.

Figure 3 Treatment effect on overall survival (A) and progression-free survival (B) by subgroup.

Table 6 Treatment-Related Adverse Events in the Groups (Matched)

	Hepa-HAIC (n=48)	HAIC group (n=48)	P
Any grade 3–4	13 (27.1)	14 (29.2)	0.820
Blood suppression
Leukopenia
Grade 1–2	14 (29.2)	12 (25.0)	0.420
Grade 3–4	1 (2.1)	2 (4.2)	1.000
Reduced hemoglobin
Grade 1–2	11 (22.9)	10 (20.8)	0.926
Grade 3–4	2 (4.2)	1 (2.1)	1.000
Thrombocytopenia
Grade 1–2	14 (29.2)	12 (25.0)	0.859
Grade 3–4	7 (14.6)	10 (20.8)	0.423
Constitutional symptom
Fever
Grade 1–2	43 (89.6)	41 (85.4)	0.537
Grade 3–4	3 (6.3)	0 (0.0)	0.241
Indigestion
Vomiting
Grade 1–2	27 (56.3)	19 (39.6)	0.102
Grade 3–4	0 (0)	3 (6.3)	0.241
Hepatic function
Elevated ALT/AST
Grade 1–2	27 (56.3)	19 (39.6)	0.102
Grade 3–4	17 (35.4)	3 (6.3)	<0.001
Elevated TBIL
Grade 1–2	20 (41.7)	10 (20.8)	0.028
Grade 3–4	11 (22.9)	20 (41.7)	0.049
Hypertension
Grade 1–2	9 (18.8)	12 (25.0)	0.493
Grade 3–4	0 (0)	0 (0)	1.000
Vomit
Grade 1–2	7 (14.6)	14 (29.2)	0.084
Grade 3–4	0 (0)	0 (0)	1.000

Note: Statistical significance was assessed with the χ² test or the Fisher’s exact test.

Abbreviations: TACE, transcatheter arterial chemoembolization; HAIC, hepatic arterial infusion chemotherapy; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin.