Hepatocellular Carcinoma with Radiological Progression: Lenvatinib Plus PD-1 Inhibitor Combined with Microwave Ablation and Synchronous Transarterial Chemoembolization

Figures & data

Figure 1 Patient flow chart.

Abbbreviations: HCC, hepatocellular carcinoma; MWA, microwave ablation; TACE, transarterial chemoembolization.

Table 1 Baseline Characteristics of the Patients with pHCC

Variable	Total (n=90)	LP-MT Group (n=42)	L-MT Group (n=48)	P
Gender				0.82
Male	80 (88.9)	37 (88.1)	43 (89.6)
Female	10 (11.1)	5 (11.9)	5 (10.4)
Age, years				0.12
≤ 60	59 (65.6)	31 (73.8)	28 (58.3)
> 60	31 (34.4)	11 (26.2)	20 (41.7)
Etiology				0.97
Hepatitis B	77 (85.6)	36 (85.7)	41 (85.4)
Other	13 (14.4)	6 (14.3)	7 (14.6)
Tumor location				0.23
Unilobar	54 (60.0)	28 (66.7)	26 (54.2)
Bilobar	36 (40.0)	14 (33.3)	22 (45.8)
Child-Pugh class				0.39
A	76 (84.4)	34 (81.0)	42 (87.5)
B	14 (15.6)	8 (19.0)	6 (12.5)
ALBI grade				0.78
1	50 (55.6)	24 (57.1)	26 (54.2)
2	40 (44.4)	18 (42.9)	22 (45.8)
Tumor size (cm)	5.5 ± 2.4	5.8 ± 2.5	5.1 ± 2.4	0.19
≤ 5	37 (41.1)	13 (31.0)	24 (50.0)
> 5	53 (58.9)	29 (69.0)	24 (50.0)
No. of tumors				0.15
Single	42 (46.7)	23 (54.8)	19 (39.6)
Multiple	48 (53.3)	19 (45.2)	29 (60.4)
PVTT				0.14
No	46 (51.1)	18 (42.9)	28 (58.3)
Yes	44 (48.9)	24 (57.1)	20 (41.7)
Extrahepatic spread				0.23
No	63 (70.0)	32 (76.2)	31 (64.6)
Yes	27 (30.0)	10 (23.8)	17 (35.4)
Laboratory test
TBIL (μmol/L)	13.7 ± 6.1	13.2 ± 6.0	14.2 ± 6.3	0.48
ALB (g/L)	39.9 ± 5.0	39.5 ± 4.9	40.2 ± 5.1	0.49
ECOG PS				0.74
0	70 (77.8)	32 (76.2)	38 (79.2)
1	20 (22.2)	10 (23.8)	10 (20.8)
BCLC stage				0.68
B	32 (35.6)	14 (33.3)	18 (37.5)
C	58 (64.4)	28 (66.7)	30 (62.5)
AFP level (ng/mL)				0.06
< 400	48 (53.3)	18 (42.9)	30 (62.5)
≥ 400	42 (46.7)	24 (57.1)	18 (37.5)

Abbreviations: LP-MT, lenvatinib plus PD-1 Inhibitor combined with microwave ablation and transarterial chemoembolization; L-MT, lenvatinib combined with microwave ablation and transarterial chemoembolization; ALBI, albumin-bilirubin; PVTT, portal vein tumor thrombosis; TBIL, total bilirubin; ALB, albumin; ECOG PS, Eastern Cooperative Oncology Group performance status; BCLC, Barcelona clinical liver cancer; AFP, α-fetoprotein.

Figure 2 Kaplan–Meier curves of progression-free survival and overall survival in the total population (a), pHCC patients with BCLC B (b) and pHCC patients with BCLC C (c).

Table 2 Overall Tumor Response in the Total and Subgroups

Response	Total			BCLC B			BCLC C
	LP-MT (n=42)	L-MT (n=48)	P	LP-MT (n=14)	L-MT (n=18)	P	LP-MT (n=28)	L-MT (n=30)	P
CR, n (%)	2 (4.8)	0 (0.0)	0.22	1 (7.1)	0 (0.0)	0.44	1 (3.6)	0 (0.0)	0.48
PR, n (%)	14 (33.3)	12 (25.0)	0.38	8 (57.1)	8 (44.4)	0.48	6 (21.4)	4 (13.3)	0.64
SD, n (%)	21 (50.0)	19 (39.6)	0.32	3 (21.4)	2 (11.1)	0.76	18 (64.3)	17 (56.7)	0.55
ORR, n (%)	16 (38.1)	12 (25.0)	0.18	9 (64.3)	8 (44.4)	0.27	7 (25.0)	4 (13.3)	0.43
DCR, n (%)	37 (88.1)	31 (64.6)	0.01	12 (85.7)	10 (55.6)	0.15	25 (89.3)	21 (70.0)	0.03

Abbreviations: LP-MT, lenvatinib plus PD-1 Inhibitor combined with microwave ablation and transarterial chemoembolization; L-MT, lenvatinib combined with microwave ablation and transarterial chemoembolization; CR, complete response; PR, partial response; SD, stable disease; ORR, objective response rate; DCR, disease control rate.

Table 3 Univariate and Multivariate Analysis of PFS and OS

Variable	Progression-Free Survival				Overall Survival
	Univariate Analysis		Multivariate Analysis		Univariate Analysis		Multivariate Analysis
	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P
Gender
Male/Female	1.38 (0.66–2.90)	0.39			1.18 (0.55–2.57)	0.26
Age, years
> 60/ ≤ 60	1.04 (0.65–1.67)	0.88			0.71 (0.30–1.69)	0.44
Treatment option
LP-MT/L-MT	0.60 (0.38–0.95)	0.03	0.53 (0.33–0.85)	0.01	0.52 (0.23–1.16)	0.11
Etiology
Other/HBV	0.94 (0.50–1.79)	0.86			1.46 (0.55–3.87)	0.45
Tumor location
Bilobar/Unilobar	1.25 (0.79–1.98)	0.34			1.22 (0.56–2.66)	0.62
Child-Pugh class
B/A	1.95 (1.07–3.57)	0.03	2.42 (1.29–4.54)	0.01	2.55 (1.07–6.09)	0.04	1.57 (0.59–4.15)	0.37
ALBI
Grade 2/1	1.29 (0.82–2.03)	0.27			4.73 (1.98–11.31)	< 0.01	3.57 (1.33–9.60)	0.01
Tumor size (cm)
> 5/≤ 5	0.77 (0.49–1.21)	0.26			1.47 (0.65–3.29)	0.35
No. of tumors
Multiple/Single	1.07 (0.68–1.67)	0.78			1.78 (0.78–4.04)	0.17
PVTT
Yes/No	1.24 (0.79–1.94)	0.35			3.32 (1.43–7.74)	0.01	2.66 (1.05–6.71)	0.04
Extrahepatic spread
Yes/No	1.45 (0.88–2.39)	0.15			1.00 (0.42–2.40)	0.99
ECOG PS
1/0	1.36 (0.78–2.36)	0.28			2.66 (1.2–5.87)	0.02	2.33 (1.01–5.38)	0.04
BCLC stage
C/B	1.44 (0.90–2.31)	0.13			1.94 (0.81–4.66)	0.14
AFP level (ng/mL)
≥ 400/< 400	1.03 (0.66–1.62)	0.90			1.92 (0.87–4.21)	0.11

Abbreviations: HR, hazard ratio; CI, confidence interval; LP-MT, lenvatinib plus PD-1 Inhibitor combined with microwave ablation and transarterial chemoembolization; L-MT, lenvatinib combined with microwave ablation and transarterial chemoembolization; HBV, hepatitis B virus; ALBI, albumin-bilirubin; PVTT, portal vein tumor thrombosis; ECOG PS, Eastern Cooperative Oncology Group performance status; BCLC, Barcelona clinical liver cancer; AFP, α-fetoprotein.

Table 4 Treatment-Related Adverse Events

Variable	Any Grade			Grade 1–2			Grade 3
	LP-MT (n=42)	L-MT (n=48)	P	LP-MT (n=42)	L-MT (n=48)	P	LP-MT (n=42)	L-MT (n=48)	P
Total	33 (78.6)	30 (62.5)	0.10	23 (54.8)	24 (50.0)	0.65	10 (23.8)	6 (12.5)	0.16
AEs related to MWA-TACE
New ascites	5 (11.9)	2 (4.2)	0.33	4 (9.5)	2 (4.2)	0.55	1 (2.4)	0 (0.0)	1.00
Liver abscess	1 (2.4)	1 (2.1)	1.00	0 (0.0)	0 (0.0)	-	1 (2.4)	1 (2.1)	1.00
Hemorrhage	0 (0.0)	1 (2.1)	1.00	0 (0.0)	0 (0.0)	-	0 (0.0)	1 (2.1)	1.00
Segmental bile duct dilatation	1 (2.4)	2 (4.2)	1.00	0 (0.0)	1 (2.1)	1.00	1 (2.4)	1 (2.1)	1.00
AEs related to drugs
Hypertension	6 (14.3)	9 (18.8)	0.57	5 (11.9)	8 (16.7)	0.52	0 (0.0)	1 (2.1)	1.00
Diarrhea	5 (11.9)	4 (8.3)	0.83	4 (9.5)	3 (6.3)	0.85	1 (2.4)	1 (2.1)	1.00
Fatigue	2 (4.8)	3 (6.3)	1.00	2 (4.8)	3 (6.3)	1.00	0 (0.0)	0 (0.0)	-
Nausea	3 (7.1)	3 (6.3)	1.00	3 (7.1)	3 (6.3)	1.00	0 (0.0)	0 (0.0)	-
Decreased appetite	5 (11.9)	7 (14.6)	0.71	4 (9.5)	6 (12.5)	0.91	1 (2.4)	1 (2.1)	1.00
Hand-foot syndrome	6 (14.3)	4 (8.3)	0.37	5 (11.9)	3 (6.3)	0.57	1 (2.4)	1 (2.1)	1.00
RCCEP	8 (19.0)	2 (4.2)	0.06	4 (9.5)	2 (4.2)	0.55	4 (9.5)	0 (0.0)	0.05
Hypothyroidism	2 (4.8)	1 (2.1)	0.91	2 (4.8)	1 (2.1)	0.91	0 (0.0)	0 (0.0)	-
Hyperthyroidism	1 (2.4)	1 (2.1)	1.00	1 (2.4)	1 (2.1)	1.00	0 (0.0)	0 (0.0)	-
Proteinuria	6 (14.3)	3 (6.3)	0.36	4 (9.5)	2 (4.2)	0.55	2 (4.8)	1 (2.1)	0.91
Elevated AST	4 (9.5)	4 (8.3)	1.00	4 (9.5)	4 (8.3)	1.00	0 (0.0)	0 (0.0)	-
Elevated ALT	7 (16.7)	5 (10.4)	0.38	7 (16.7)	5 (10.4)	0.38	0 (0.0)	0 (0.0)	-
Elevated TBIL	3 (7.1)	4 (8.3)	1.00	3 (7.1)	4 (8.3)	1.00	0 (0.0)	0 (0.0)	-
Leukocytopenia	1 (2.4)	5 (10.4)	0.27	1 (2.4)	4 (8.3)	0.44	0 (0.0)	1 (2.1)	1.00

Abbreviations: LP-MT, lenvatinib plus PD-1 Inhibitor combined with microwave ablation and transarterial chemoembolization; L-MT, lenvatinib combined with microwave ablation and transarterial chemoembolization; AEs, adverse events; MWA-TACE, microwave ablation and transarterial chemoembolization; RCCEP, reactive cutaneous capillary endothelial proliferation; AST, aspartate aminotransferase; ALT, alanine aminotransferase; TBIL, total bilirubin.

Data Sharing Statement

The data used in this study are available from the corresponding author on reasonable request.