PD-1 Inhibitors Combined with Antiangiogenic Therapy with or Without Transarterial Chemoembolization in the Treatment of Hepatocellular Carcinoma: A Propensity Matching Analysis

Figures & data

Table 1 Baseline Characteristics of the Patients Before and After PSM

Variable	Before PSM			After PSM
	Triple Therapy Group	Control Group	P	Triple Therapy Group	Control Group	P
Patients	62	83		46	46
Male sex	55(0.89)	71(0.86)	0.576	41(0.89)	42(0.91)	0.726
Age ≥ 65 years	12(0.19)	37(0.45)	0.141	9(0.20)	11(0.24)	0.613
Child–Pugh			0.975			0.769
A	48(0.77)	65(0.78)		35(0.76)	32(0.70)
B	13(0.21)	17(0.20)		10(0.22)	13(0.28)
C	1(0.02)	1(0.01)		1(0.02)	1(0.02)
Number of tumors ≥ 2	46(0.74)	60(0.72)	0.798	36(0.78)	34(0.74)	0.625
Tumor diameter> 5cm	48(0.77)	59(0.71)	0.580	34(0.74)	33(0.72)	0.815
AFP	38(0.61)	40(0.48)	0.118	27(0.59)	27(0.59)	1
ALP levels ≥ 125 U/L	32(0.52)	51(0.61)	0.236	27(0.59)	25(0.54)	0.674
Platelet count ≥ 100 × 109/L	42(0.68)	63(0.76)	0.277	32(0.70)	30(0.65)	0.656
ALT levels ≥ 40 U/L	29(0.47)	45(0.54)	0.375	24(0.52)	22(0.48)	0.677
Leukocyte ≥ 4 × 109/L	52(0.84)	81(0.98)	0.781	39(0.85)	40(0.87)	0.765
BCLC stage			0.731			0.926
A	6(0.10)	6(0.07)		3(0.07)	4(0.09)
B	9(0.15)	8(0.10)		5(0.11)	6(0.13)
C	46(0.74)	68(0.82)		37(0.80)	35(0.76)
D	1(0.02)	1(0.01)		1(0.02)	1(0.02)
Portal vein invasion	28(0.45)	43(0.52)	0.428	25(0.54)	24(0.52)	0.834
HBV	46(0.74)	58(0.70)	0.568	34(0.74)	35(0.76)	0.810
Lymph node metastasis	26(0.42)	41(0.49)	0.373	21(0.46)	22(0.48)	0.834
Extrahepatic metastases	14(0.23)	32(0.39)	0.041	13(0.28)	15(0.33)	0.650

Abbreviations: PSM, propensity score matching; AFP, alpha fetoprotein; ALP, alkaline phosphatase; ALT, alanine aminotransferase; BCLC, Barcelona Clinic Liver Cancer; HBV, hepatitis B virus.

Figure 1 Kaplan-Meier plots: The triple therapy group exhibited longer mOS and mPFS than that of the control group before (a and b) and after (c and d) PSM.

Table 2 Analyses of Prognostic Factors for Survival After PSM

Factor	Overall Survival
	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	P	HR (95% CI)	P
Sex (male/female)	0.496(0.193–0.273)	0.145
Age (≥65/<65 years)	1.337(0.72–2.484)	0.357
Child-Pugh class (A/B/C)		0.481
A	1.000
B	1.281(0.694–2.365)	0.429
C	2.088(0.498–8.756)	0.314
Number of tumors (≥2/<2)	1.608(0.848–3.049)	0.146
Tumor diameter (≥5/<5 cm)	1.466(0.775–2.774)	0.239
AFP (≥400/<400 ng/mL)	2.435(1.307–4.537)	0.005	2.046(1.068–3.918)	0.031
ALP (≥125/<125 U/L)	3.248(1.755–6.014)	<0.001	2.579(1.341–4.96)	0.005
Platelet (<100,000/≥100,000/mL)	1.546(0.829–2.883)	0.171
ALT (≥40/<40U/L)	1.112(0.639–1.935)	0.708
Leukocyte (<4000/≥4000/mL)	1.758(0.697–4.432)	0.232
HBV (positive/negative)	1.913(0.974–3.758)	0.06
Portal vein invasion (yes/no)	2.08(1.147–3.77)	0.016	1.5(0.797–2.822)	0.208
BCLC		0.065
A	1.000
B	1.245(0.175–8.883)	0.827
C	4.298(1.025–18.014)	0.046
D	6.979(0.959–50.804)	0.055
Lymph node metastasis (yes/no)	1.335(0.765–2.329)	0.31
Extrahepatic metastases (yes/no)	1.135(0.636–2.025)	0.668
Triple therapy (Yes/No)	0.477(0.271–0.842)	0.011	0.385(0.215–0.689)	0.001

Abbreviations: PSM, propensity score matching; HR, hazard ratio; AFP, alpha fetoprotein; ALP, alkaline phosphatase; ALT, alanine transaminase; HBV, hepatitis B virus; BCLC, Barcelona ClinicLiver Cancer.

Table 3 Analyses of Prognostic Factors for Progression-Free Survival After PSM

Factor	Progression-Free Survival
	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	P	HR (95% CI)	P
Sex (male/female)	1.058(0.456–2.455)	0.896
Age (≥65/<65 years)	0.927(0.53–1.621)	0.791
Child-Pugh class (A/B/C)		0.753
A	1
B	1.056(0.256–4.358)	0.94
C	1.286(0.299–5.527)	0.736
Number of tumors (≥2/<2)	1.597(0.918–2.781)	0.098
Tumor diameter (≥5/<5 cm)	1.784(1.027–3.097)	0.04	1.062(0.55–2.051)	0.858
AFP (≥400/<400 ng/mL)	0.818(0.51–1.31)	0.403
ALP (≥125/<125 U/L)	1.739(1.073–2.819)	0.025	1.202(0.705–2.049)	0.499
Platelet (<100,000/≥100,000/mL)	1.658(0.982–2.799)	0.059
ALT (≥40/<40U/L)	1.119(0.701–1.787)	0.637
Leukocyte (<4000/≥4000/mL)	1.604(0.767–3.355)	0.209
HBV (positive/negative)	1.264(0.738–2.165)	0.394
Portal vein invasion (yes/no)	1.758(1.086–2.845)	0.022	1.149(0.673–1.962)	0.611
BCLC		0.016		0.204
A	1		1
B	0.457(0.083–2.525)	0.369	0.627(0.099–3.984)	0.621
C	0.378(0.069–2.079)	0.264	0.495(0.079–3.095)	0.452
D	1.404(0.342–5.766)	0.638	1.504(0.322–7.019)	0.604
Lymph node metastasis (yes/no)	1.302(0.816–2.077)	0.268
Extrahepatic metastases (yes/no)	0.88(0.528–1.466)	0.624
Triple therapy (Yes/No)	0.644(0.401–1.033)	0.068

Abbreviations: PSM, propensity score matching; HR, hazard ratio; AFP, alpha fetoprotein; ALP, alkaline phosphatase; ALT, alanine transaminase; HBV, hepatitis B virus; BCLC, Barcelona Clinic Liver Cancer.

Figure 2 Survival curve of AFP (≥ 400ng/mL/<400ng/mL) group (a), ALP (≥ 125u/L/< 125u/L) group (b), PVTT group (c).

Data Sharing Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author (Lanpaoxiansheng @126.com).