Efficacy and safety of transcatheter arterial chemoembolization followed by hepatic arterial infusion chemotherapy combined with TKI and PD-1 inhibitors as first-line treatment for advanced hepatocellular carcinoma

doi:10.12122/j.issn.1673-4254.2024.09.24

Abstract

Abstract:

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) followed by hepatic arterial infusion chemotherapy (HAIC) combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma (HCC). Methods We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July, 2020 and June, 2023. 23 of the patients received TACE combined with HAIC and TKI (TACE+HAIC+TKI group) and 47 received TACE combined with HAIC, PD-1 inhibitors and TKI (TACE+HAIC+PD-1+TKI group). The clinical characteristics, laboratory test results, efficacy, outcomes and adverse events of the patients were compared between the two groups. Results The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates (ORR; 60.87% vs 36.17%, P=0.031), comparable disease control rates (95.65% vs 93.62%, P=0.068), and different median progression-free survival (PFS) time (10.2 vs 11.8 months, P=0.003) and median overall survival (OS) time (15.7 vs 19.5 months, P=0.035). After propensity score matching (PSM), the median PFS and OS time of the two groups was 10.1 vs 14.5 months (P=0.024) and 14.2 vs 21.2 months (P=0.221), respectively. The 1-year PFS rates of the 2 groups were 24.0% vs 52.2%, and the 1-, 2- and 3-year OS rates were 72.3% vs 93.1%, 23.9% vs 63.8%, and 23.9% vs 36.5%, respectively. The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group (21.28% vs 0, P=0.025), but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups. Conclusion The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

Key words: advanced hepatocellular carcinoma, progression-free survival, overall survival, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, TKI, PD-1 inhibitors

Liping ZHANG, Xijuan LIU, Xiao HU, Jiali WANG, Xihe YU, Guoliang LI, Haimin YOU, Qizhou ZHANG, Haibo ZHANG. Efficacy and safety of transcatheter arterial chemoembolization followed by hepatic arterial infusion chemotherapy combined with TKI and PD-1 inhibitors as first-line treatment for advanced hepatocellular carcinoma[J]. Journal of Southern Medical University, 2024, 44(9): 1831-1838.

Figures/Tables 8

References 25

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Item	TACE+HAIC+TKI (n=23)	TACE+HAIC+PD-1+TKI (n=47)	P
Gender			0.207
Male	16 (69.56%)	39 (82.98%)
Female	7 (30.44%)	8 (17.02%)
Age (years)	63.2	53.6	<0.001
CNLC Stage			<0.001
II	12 (52.17%)	3 (6.38%)
III	11 (47.83%)	44 (93.62%)
Tumor diameter (cm)			0.216
<10	20 (86.96%)	33 (70.21%)
>10	3 (13.04%)	14 (29.79%)
PVTT			0.042
No	15 (65.22%)	17 (36.17%)
Yes	8 (34.78%)	30 (63.83%)
Extrahpatic M			0.031
>3	5 (21.74%)	23 (48.94%)
1-3	3 (13.04%)	9 (19.15%)
0	15 (65.22%)	15 (31.91%)
Hepatitis			1.000
Hepatitis B	22 (95.65%)	44 (93.62%)
Hepatitis C	0 (0.00%)	1 (2.13%)
No	1 (4.35%)	2 (4.26%)
C-P classification			0.725
A	14 (60.87%)	25 (53.19%)
B	9 (39.13%)	22 (46.81%)
ECOG score			0.217
0	1 (4.35%)	0 (0.00%)
1	12 (52.17%)	31 (65.96%)
2	10 (43.48%)	16 (34.04%)
KPS score			0.551
60	0 (0.00%)	1 (2.13%)
70	3 (13.04%)	7 (14.89%)
80	14 (60.87%)	33 (70.21%)
90	6 (26.09%)	6 (12.77%)
TACE/HAIC cycle	3.00 (2.0; 4.0)	3.00 (2.0; 4.0)	0.948

Item	TACE+HAIC+TKI (n=23)	TACE+HAIC+PD-1+TKI (n=47)	P
Gender			0.207
Male	16 (69.56%)	39 (82.98%)
Female	7 (30.44%)	8 (17.02%)
Age (years)	63.2	53.6	<0.001
CNLC Stage			<0.001
II	12 (52.17%)	3 (6.38%)
III	11 (47.83%)	44 (93.62%)
Tumor diameter (cm)			0.216
<10	20 (86.96%)	33 (70.21%)
>10	3 (13.04%)	14 (29.79%)
PVTT			0.042
No	15 (65.22%)	17 (36.17%)
Yes	8 (34.78%)	30 (63.83%)
Extrahpatic M			0.031
>3	5 (21.74%)	23 (48.94%)
1-3	3 (13.04%)	9 (19.15%)
0	15 (65.22%)	15 (31.91%)
Hepatitis			1.000
Hepatitis B	22 (95.65%)	44 (93.62%)
Hepatitis C	0 (0.00%)	1 (2.13%)
No	1 (4.35%)	2 (4.26%)
C-P classification			0.725
A	14 (60.87%)	25 (53.19%)
B	9 (39.13%)	22 (46.81%)
ECOG score			0.217
0	1 (4.35%)	0 (0.00%)
1	12 (52.17%)	31 (65.96%)
2	10 (43.48%)	16 (34.04%)
KPS score			0.551
60	0 (0.00%)	1 (2.13%)
70	3 (13.04%)	7 (14.89%)
80	14 (60.87%)	33 (70.21%)
90	6 (26.09%)	6 (12.77%)
TACE/HAIC cycle	3.00 (2.0; 4.0)	3.00 (2.0; 4.0)	0.948

Group	ORR	DCR	P
TACE+HAIC+TKI (n=23)	60.87% (14/23)	95.65% (22/23)	0.031
TACE+HAIC+PD-1+TKI (n=47)	36.17% (17/47)	93.62% (44/47)	0.068

Group	ORR	DCR	P
TACE+HAIC+TKI (n=23)	60.87% (14/23)	95.65% (22/23)	0.031
TACE+HAIC+PD-1+TKI (n=47)	36.17% (17/47)	93.62% (44/47)	0.068

Group	1 year-PFS (95% CI)	2 years-PFS (95% CI)
TACE+HAIC+TKI (n=23)	24.0% (11.2%, 51.4%)	NA
TACE+HAIC+PD-1+TKI (n=47)	52.2% (39.2%, 69.5%)	16.4% (7.3%, 36.7%)