Simultaneous and Sequential Use of Molecular Targeted Agents Plus Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Real-World Practice in China

Figures & data

Table 1 Demographic and Clinical Characteristics in the Two Groups

	Simultaneous Group (n=64)	Sequential Group (n=46)	P value
Gender			0.20
Male	58 (90.6%)	36 (78.3%)
Female	6 (9.4%)	10 (21.7%)
Age (years)	54.7±12.8	58.2±11.8	0.30
ECOG PS
0	56 (87.5%)	40 (87.0%)	0.94
1	8 (12.5%)	6 (13.0%)
Viral hepatitis background			0.39
HBV	54 (84.4%)	44 (95.7%)
HCV	2 (3.1%)	0
None	8 (12.5%)	2 (4.3%)
WBC (×10^9/L)	5.8±2.2	5.3±2.3	0.44
Hb (g/L)	132.5±26.1	123.4±27.6	0.22
PLT (×10^9/L)	165.8±82.2	150.7±78.5	0.50
TB (μmol/L)	18.2±10.2	14.2±8.7	0.13
ALB (g/L)	38.5±5.7	39.3±4.7	0.56
ALT (IU/L)	48.9±27.4	36.0±17.5	0.06
AFP			0.84
<200 μg/mL	30 (46.9%)	20 (43.5%)
≥200 μg/mL	34 (53.1%)	23 (56.5%)
Child-Pugh scores			0.18
5	50 (78.1%)	32 (69.6%)
6	14 (21.9%)	14 (30.4%)
Total tumor size (cm)	7.4±5.7	6.8±5.1	0.24
Tumor number			0.46
≤3	20 (31.2%)	14 (30.4%)
>3	44 (68.8%)	32 (69.6%)
Macrovascular invasion			0.14
Yes	26 (40.6%)	10 (21.7%)
No	38 (59.4%)	36 (78.3%)
Extrahepatic metastasis			0.76
Yes	22 (34.4%)	14 (30.4%)
No	42 (65.6%)	32 (69.6%)
MTAs			0.09
Sorafenib	20 (31.2%)	20 (43.5%)
Lenvatinib	44 (68.8%)	26 (56.5%)
ICIs			0.36
Pembrolizumab	6 (9.4%)	6 (13.0%)
Sintilimab	58 (90.6%)	40 (87.0%)
Concurrent treatments			0.12
HAIC	6	4
TACE	32	20
Radiotherapy	2	4

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; HBV, hepatitis B virus; HCV, hepatitis C virus; WBC, white blood cell; Hb, hemoglobin; PLT, platelet; TB, total bilirubin; ALB, albumin; ALT, alanine aminotransferase; AFP, alpha-fetoprotein; MTAs, molecular targeted agents; ICIs, immune checkpoint inhibitors; HAIC, hepatic artery infusion chemotherapy; TACE, transarterial chemoembolization.

Table 2 Treatment Related Adverse Events (CTCAE V. 5.0)

Adverse Event	Total	Simultaneous Group		Sequential Group
	Any Grade n (%)	Grade 1/2	Grade 3/4	Grade 1/2	Grade 3/4
Hand-foot skin reaction	24 (21.8%)	14	0	10	0
Diarrhea	20 (18.2%)	10	0	10	0
Fatigue	20 (18.2%)	16	0	4	0
Hypertension	18 (16.4%)	12	0	6	0
Hepatic toxicity	12 (10.9%)	5	1	6	0
Renal toxicity	6 (5.4%)	3	0	3	0
Upper gastrointestinal bleeding	6 (5.4%)	0	4	0	2
Pneumonia	4 (3.6%)	3	0	1	0
Myasthenia gravis	2 (1.8%)	0	1	0	1
Allergy	2 (1.8%)	1	0	1	0

Table 3 Treatment Responses and Survival Outcomes in the Two Groups

	Simultaneous Group (n=64)	Sequential Group (n=46)	P value
Tumor response			0.12
CR	4	0
PR	12	2
SD	28	18
PD	20	26
ORR	25.0% (16)	4.3% (2)	0.04
DCR	68.8% (44)	43.5% (20)	0.06
Median OS (months)	16.3	12.5	0.22
OS rate			0.35
At 6 months	83.7%	72.2%
At 12 months	73.2%	45.9%

Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate; OS, overall survival.

Figure 1 Kaplan-Meier estimates of overall survival in the two groups of patients treated with molecular targeted agents plus immune checkpoint inhibitors.

Figure 2 Uni- and multivariate analysis of possible factors associated with survival of patients treated with molecular targeted agents plus immune checkpoint inhibitors.