Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China

Table 1 Characteristics of patients with advanced hepatocellular carcinoma treated with lenvatinib

	All (n = 54)	HBV-related HCC (n = 40)
Age, yr	58.94 ± 12.10	57.49 ± 12.03
Gender (male:female)	46:8	35:5
Height, cm	172.04 ± 7.65	171.72 ± 7.24
Weight, kg	70.47 ± 13.72	69.21 ± 12.35
Etiology (HBV:HCV:Others)	40:5:9	40
Total bilirubin, mg/dL	29.81 ± 31.35	32.40 ± 33.17
Albumin, g/dL	38.53 ± 5.64	38.73 ± 5.01
Prothrombin time, positive, %	14 (26%)	10 (25%)
Extrahepatic spread	18 (33.3%)	12 (30%)
Lymphatic metastasis	33 (61%)	28 (70%)
Liver occupation (< 50%: > 50%)	38:15	27:13
Portal vein thrombus	21 (39%)	16 (40%)
Baseline AFP (ng/mL)(≥ 200: < 200)	32:22	22:18
Native: Recurrence	28:26	19:21
History of treatment (TACE: RFA: Targeted therapy)	37:21:17	29:14:14
History of Radiotherapy	11 (20%)	7 (18%)
Initial dose of LEN (8 mg: 12 mg)	26:28	21:19
Diagnostic method (Image: Pathology)	25:29	21:19
Size of target lesion, cm	6.93 ± 4.75	7.25 ± 4.36

AFP: α-fetoprotein; HBV: Hepatitis B virus; EHS: Extrahepatic spread; HCV: Hepatitis C virus; LEN: Lenvatinib; TACE: Transcatheter arterial chemoembolization; RFA: Radiofrequency ablation.

Table 2 Combination characteristics of patients with advanced hepatocellular carcinoma treated with lenvatinib

	All (n = 54)	HBV-related HCC (n = 40)
ECOG PS (0: 1: 2)	11:38:5	9:28:3
Child-Pugh score (5: 6: 7: 8)	29:15:7:3	21:13:4:2
ALBI grade (1: 2: 3)	27:25:2	20:19:1
BCLC stage (B: C)	18:36	12:28
TNM stage (IIIA: IIIB: IVA: IVB)	8:7:18:21	3:6:16:15

ECOG: Eastern Cooperative Oncology Group; PS: Performance Status; ALBI grade: Albumin-bilirubin grade; BCLC: Barcelona Clinic Liver Cancer; HBV: Hepatitis B virus; TNM: Tumor node metastasis; aHCC: Advanced hepatocellular carcinoma.

Table 3 Efficacy of lenvatinib in patients with advanced hepatocellular carcinoma

Investigator review according to RECIST 1.1	ALL (n = 54)	HBV-related HCC (n = 40)	P value
Progression-free survival (d, 95%CI)	168 (130-205)	175 (124-226)	0.250
Time to progression (d, 95%CI)	153 (116-189)	156 (126-186)	0.520
Objective response	22%	25%	0.753
Complete response	0	0	-
Partial response	12	10	-
Stable disease	36	26	0.866
Progressive disease	6	4	-
Disease control rate	88%	90%	0.863
Decreased AFP predicts tumor reduction
Se	56.7%	53.8%	-
Sp	83.3%	85.7%	-

HBV: Hepatitis B virus; RECIST 1.1: Response Evaluation Criteria in Solid Tumors version 1.1; AFP: Alpha-fetoprotein; Se: Sensitivity; Sp: Specificity; CI: Confidence interval.

Table 4 Lenvatinib-related adverse events in patients with hepatocellular carcinoma, n (%)

Event	Hepatocellular carcinoma (n = 56)
	Any grade	Grade 3-4
Any adverse event	52 (92.9)	11 (21.2)
Hypertension	25 (44.6)	2 (3.8)
Fatigue	10 (17.9)	0
Decreased appetite	13 (23.2)	1 (1.9)
Diarrhea	13 (23.2)	2 (3.8)
Proteinuria	12 (21.4)	5 (9.6)
Decreased weight	3 (5.4)	0
Hand-foot skin reaction	6 (10.7)	0
Nausea	5 (8.9)	0
Abdominal pain	4 (7.1)	0
Rash	4 (7.1)	1 (1.9)
Decreased platelet count	3 (5.4)	0
Vomiting	1 (1.8)	0
Hypothyroidism	2 (3.6)	0
Dysphonia	1 (1.8)	0

Table 5 Multivariate analysis of the objective response rate and progression-free survival in patients with advanced hepatocellular carcinoma treated with lenvatinib

Clinical factors	Category	Analysis of ORR		Analysis of PFS
		P value	OR, 95%CI	P value	HR, 95%CI
Age (yr)	< 58.8	0.489	0.978 (0.919-1.041)	0.010	0.959 (0.929-0.990)
Gender	Male	0.571	1.828 (0.227-14.724)	0.606	1.137 (0.698-1.850)
HBV infection	HBV	0.371	2.300 (0.370-14.290)	0.151	1.844 (0.799-4.257)
First-line therapy	Sorafenib	0.212	0.324 (0.055-1.901)	0.167	1.724 (0.796-3.734)
Extrahepatic spread	Without	0.604	0.600 (0.088-4.118)	0.443	0.675 (0.247-1.844)
Tumor occupation	< 50%	0.937	1.080 (0.162-7.178)	0.169	2.043 (0.738-5.654)
Portal vein thrombus	Without	0.987	0.985 (0.167-5.817)	0.037	0.381 (0.154-0.944)
History of TACE	With	0.396	2.229 (0.350-14.186)	0.776	0.875 (0.348-2.197)
Combination factors
ECOG-PS score	0	0.066	3.571 (0.876-14.564)	0.05	4.9 (0.998-24.193)
ALBI stage	1	0.651	-	0.462	0.574 (0.130-2.524)
Child-Pugh class	A	0.061	-	0.042	0.468 (0.225-0.973)
BCLC stage	B	0.487	1.593 (0.425-5.971)	0.031	0.465 (0.232-0.931)

ECOG: Eastern Cooperative Oncology Group; PS: Performance Status; ALBI grade: Albumin-bilirubin grade; BCLC: Barcelona Clinic Liver Cancer; TACE: Transarterial chemoembolization; HBV: Hepatitis B virus; HCV: Hepatitis C virus; EHS: Extrahepatic spread; ORR: Objective response rate; PFS: Progression-free survival; OR: Odds ratio; HR: Hazard ratio.