Hepatic Arterial Infusion Chemotherapy Combined with Lenvatinib Plus Humanized Programmed Death Receptor-1 in Patients with High-Risk Advanced Hepatocellular Carcinoma: A Real-World Study

Figures & data

Figure 1 (A) Flowchart of the patient cohort. (B) The schema of the combination therapy.

Table 1 Baseline Characteristics of 97 Patients

Characteristics	Patients
Gender
Male	85 (87.6)
Female	12 (12.4)
Age
Median	57 (38–76)
ECOG score
0	72 (74.2)
1	21 (21.7)
2	4 (4.1)
Child-Pugh
A	80 (82.5)
B	17 (17.5)
Viral status
Uninfected	10 (10.3)
HBV	85 (87.6)
HCV	2 (2.1)
Tumor size, cm
Median (IQR)	12.7 (8.3–16.7)
Portal vein invasion
Absent	15 (14.4)
Present	82 (84.6)
VP1-2	3 (3.1)
VP3	14 (14.4)
VP4	65 (67.1)
Venous invasion
Absent	72 (74.2)
Present	25 (25.8)
Extrahepatic spread
Absent	66 (68.1)
Present	31 (31.9)
AFP, ng/mL
≤400	29 (29.9)
>400	68 (70.1)
High-risk type
VP4	52 (53.6)
Tumor involvement >50%	31 (32.0)
Both	14 (14.4)
PD-1 inhibition agent
Camrelizumab	57 (58.7)
Tislelizumab	25 (25.8)
Sintilimab	15 (15.5)
ALBI
1	52 (53.6)
2	45 (46.4)
PCT, ng/mL
≤0.13	40 (41.3)
>0.13	57 (58.7)

Table 2 Summary of Best Response

	RECIST	mRECIST
Overall Response
Complete response	0	16 (16.5)
Partial response	63 (64.9)	60 (61.9)
Stable disease	27 (27.9)	14 (14.4)
Progressive disease	7 (7.2)	7 (7.2)
Objective response rate	63 (64.9)	76 (78.3)
Disease control rate	90 (92.8)	90 (92.8)
Intrahepatic Response
Complete response	0	18 (18.5)
Partial response	65 (67.0)	61 (62.9)
Stable disease	29 (29.9)	15 (15.5)
Progressive disease	3 (3.1)	3 (3.1)
Objective response rate	61 (67.0)	79 (81.4)
Disease control rate	94 (96.9)	94 (96.9)

Figure 2 Kaplan–Meier curves of PFS ((A) n=97), OS ((B) n=97), DOR ((C) n=76), and intrahepatic DOR ((D) n=79).

Figure 3 Kaplan-Meier plots show percent OS categorized by (A) ALBI, (B) BMI, (C) High-risk type, (D) Metastasis, (E) Child-Pugh class, and (F) PD-1 agents, with numbers at risk shown below the graph.

Figure 4 Percentage changes from baseline. (A) Best percentage change from baseline in intrahepatic target lesion per RECIST 1.1. The dashed line at 30% change represents the partial response. (B) Best percentage change from baseline in intrahepatic target lesion per mRECIST. The dashed line at 30% change represents the partial response.

Table 3 Univariable and Multivariable Analyses of Covariates Associated with PFS

Variables	Univariable Analysis			Multivariable Analysis
	HR	95% CI	P-value	HR	95% CI	p-value
Gender (Male vs Female)	0.679	0.345–1.337	0.263
Age (<60 vs ≥60)	0.574	0.338–0.976	0.041	0.632	0.371–1.076	0.091
AFP (≤400 vs.>400 ng/mL)	0.926	0.555–1.545	0.769
Child-Pugh class (A vs B)	1.642	0.919–2.932	0.094	0.695	0.345–1.401	0.309
ALBI (Grade 1 vs Grade 2)	1.800	1.100–2.945	0.019	1.748	1.028–2.972	0.039
HBV infected (No vs Yes)	1.168	0.553–2.464	0.684
Extrahepatic metastasis (No vs Yes)	2.013	1.209–3.352	0.007	1.670	0.977–2.853	0.061
Vp4 (No vs Yes)	0.674	0.402–1.131	0.135	1.132	0.521–2.456	0.755
TO≥50% (No vs Yes)	1.910	1.166–3.129	0.010	1.590	0.752–3.361	0.225
PCT (≤0.13 vs.>0.13 ng/mL)	2.272	1.598–4.654	0.001	2.397	1.325–4.334	0.004

Note: Bold text indicates variable with p<0.05.

Table 4 Univariable and Multivariable Analyses of Covariables Associated with OS

Variable	Univariable Analysis			Multivariable Analysis
	HR	95% CI	p-value	HR	95% CI	p-value
Gender (Male vs Female)	0.392	0.179–0.856	0.019	0.287	0.121–0.676	0.004
Age (<60 vs ≥60)	0.735	0.377–1.431	0.365
AFP (≤400 vs.>400 ng/mL)	0.928	0.483–1.783	0.822
Child-Pugh class (A vs B)	2.128	1.076–4.207	0.030	0.955	0.410–2.225	0.915
ALBI (Grade 1 vs Grade 2)	1.784	0.935–3.402	0.079	1.810	0.849–3.855	0.124
HBV infected (No vs Yes)	0.754	0.329–1.172	0.503
Extrahepatic metastasis (No vs Yes)	2.307	1.217–4.373	0.010	1.916	0.951–3.859	0.069
Vp4 (No vs Yes)	0.914	0.450–1.854	0.803
TO≥50% (No vs Yes)	1.667	0.882–3.149	0.115	1.134	0.547–2.351	0.735
PCT (≤0.13 vs.>0.13 ng/mL)	3.788	1.776–8.079	0.001	3.226	1.396–7.451	0.006

Note: Bold text indicates variable with p<0.05.

Table 5 Treatment-Related Adverse Events

Adverse Event*	Any Grade	Grade 1–2	Grade 3–4
Neutropenia	35 (36.1%)	30 (30.9%)	5 (5.2%)
Anemia	13 (13.4%)	11 (11.3%)	2 (2.1%)
Thrombocytopenia	43 (44.3%)	36 (37.1%)	7 (7.2%)
Fatigue	43 (44.3%)	40 (41.2%)	3 (3.1%)
Hypertension	52 (53.6%)	43 (44.3%)	9 (9.3%)
Weight loss	38 (39.2%)	36 (37.1%)	2 (2.1%)
Hypothyroidism	36 (37.1%)	33 (34.0%)	3 (3.1%)
Hand foot skin reaction	10 (10.3%)	9 (9.3%)	1 (1.0%)
Rash	18 (18.6%)	13 (13.4%)	5 (5.2%)
Vomiting	30 (30.9%)	25 (25.7%)	5 (5.2%)
Diarrhea	32 (33.0%)	28 (28.9%)	4 (4.1%)
Abdominal pain	42 (43.3%)	41 (42.3%)	1 (1.0%)
Proteinuria	29 (29.9%)	24 (24.8%)	5 (5.1%)
Elevated ALT	62 (63.9%)	55 (56.7%)	7 (7.2%)
Elevated AST	65 (67.0%)	57 (58.8%)	8 (8.2%)
Hyperbilirubinemia	23 (23.7%)	18 (18.6%)	5 (5.1%)
Hypoalbuminemia	28 (28.9%)	25 (25.8%)	3 (3.1%)
Sensory neuropathy	11 (11.3%)	11 (11.3%)	0
Decreased appetite	27 (27.8%)	24 (24.7%)	3 (3.1%)
Elevated creatinine	18 (18.6%)	14 (14.5%)	4 (4.1%)
Immune-related hepatitis	4 (4.1%)	2 (2.1%)	1 (1.0%)
Immune-related pneumonitis	2 (2.1%)	0	2 (2.1%)
Immune-related dermatitis	8 (8.2%)	7 (7.2%)	2 (1.0%)

Note: *Listed are adverse events, as defined by the National Cancer Institute Common Terminology Criteria (version 4.03).

Figure 5 The levels of PCT before the treatment might be a predictive biomarker for the efficacy of combination therapy. Kaplan–Meier curves of PFS (A) and OS (B) between high- and low-PCT groups.