CRAFITY score and nomogram predict the clinical efficacy of lenvatinib combined with immune checkpoint inhibitors in hepatocellular carcinoma

Table 1 Baseline characteristics, n (%)

Characteristics	Overall (n = 192)	CRAFITY-high (n = 40)	CRAFITY-intermediate (n = 102)	CRAFITY-low (n = 50)	P value
Age, median [IQR]	57.5 [50.0, 64.0]	61.0 [55.0, 64.0]	56.0 [50.0, 62.0]	56.5 [50.2, 64.0]	0.0746
Sex					0.5933
Male	161 (83.9)	33 (82.5)	88 (86.3)	40 (80.0)
Female	31 (16.1)	7 (17.5)	14 (13.7)	10 (20.0)
ECOG PS					0.0071
0	114 (59.4)	20 (50.0)	55 (53.9)	39 (78.0)
1	78 (40.6)	20 (50.0)	47 (46.1)	11 (22.0)
Cause					0.2466
HBV	166 (86.5)	38 (95.0)	85 (83.3)	43 (86.0)
HCV	15 (7.8)	2 (5.0)	8 (7.8)	5 (10.0)
Others	11 (5.7)	0 (0.0)	9 (8.8)	2 (4.0)
Cirrhosis	160 (83.3)	35 (87.5)	85 (83.3)	40 (80.0)	0.6376
Resection	30 (15.6)	4 (10.0)	19 (18.6)	7 (14.0)	0.4153
TACE	166 (86.5)	31 (77.5)	87 (85.3)	48 (96.0)	0.0343
Ablation	80 (41.7)	12 (30.0)	46 (45.1)	22 (44.0)	0.241
Treatment line					0.505
First	147 (76.6)	33 (82.5)	78 (76.5)	36 (72.0)
Later	45 (23.4)	7 (17.5)	24 (23.5)	14 (28.0)
Number					0.2285
< 3	73 (38.0)	13 (32.5)	36 (35.3)	24 (48.0)
≥ 3	119 (62.0)	27 (67.5)	66 (64.7)	26 (52.0)
Size					0.0149
< 5 cm	66 (34.4)	6 (15.0)	40 (39.2)	20 (40.0)
≥ 5 cm	126 (65.6)	34 (85.0)	62 (60.8)	30 (60.0)
PVTT	101 (52.6)	28 (70.0)	45 (44.1)	28 (56.0)	0.018
EHM	90 (46.9)	18 (45.0)	51 (50.0)	21 (42.0)	0.627
Child-Pugh					0.9888
Grade A	128 (66.7)	27 (67.5)	68 (66.7)	33 (66.0)
Grade B	64 (33.3)	13 (32.5)	34 (33.3)	17 (34.0)
BCLC					0.1836
Stage B	34 (17.7)	5 (12.5)	16 (15.7)	13 (26.0)
Stage C	158 (82.3)	35 (87.5)	86 (84.3)	37 (74.0)

ECOG PS: Eastern Cooperative Oncology Group performance status; HBV: Hepatitis B virus; HCV: Hepatitis C virus; TACE: Transarterial chemoembolization; PVTT: Portal vein tumor thrombosis; EHM: Extrahepatic metastasis; BCLC: Barcelona Clinic Liver Cancer.

Table 2 Efficacy according to CRAFITY score, n (%)

	All (n = 192)	CRAFITY-high (n = 40)	CRAFITY-intermediate (n = 102)	CRAFITY-low (n = 50)	P value
PFS, months (95%CI)	5.2 (4.1-6.2)	3.1 (2.7-4.1)	6.0 (4.3-6.8)	8.4 (5.2-11.7)	< 0.0001
OS, months (95%CI)	17.7 (15.8-26.3)	6.6 (4.1-NR)	19.2 (15.8-26.8)	33.4 (21.4-NR)	< 0.0001
Initial response					0.0277
CR	3 (1.5)	0 (0.0)	2 (2.0)	1 (2.0)
PR	30 (15.6)	2 (5.0)	18 (17.6)	10 (20.0)
SD	105 (54.7)	18 (45.0)	58 (56.9)	29 (58.0)
PD	54 (28.1)	20 (50.0)	24 (23.5)	10 (20.0)
ORR	33 (17.1)	2 (5.0)	20 (19.6)	11 (22.0)	0.0669
DCR	138 (71.9)	20 (50.0)	78 (76.5)	40 (80.0)	0.0023

PFS: Progression-free survival; OS: Overall survival; CI: Confidence interval; NR: Not reach; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; ORR: Objective response rate; DCR: Disease control rate.

Table 3 Univariate Cox regression for progression-free survival and overall survival (95% confidence interval)

Characteristic	PFS, HR	PFS, P value	OS, HR	OS, P value
CRAFITY (intermediate vs high)	0.48 (0.32-0.72)	< 0.001	0.35 (0.21-0.58)	< 0.001
CRAFITY (low vs high)	0.33 (0.21-0.54)	< 0.001	0.21 (0.11-0.4)	< 0.001
Sex (male vs female)	0.83 (0.55-1.24)	0.359	1.54 (0.82-2.9)	0.181
Age (≥ 60 years vs <60 years)	0.82 (0.6-1.13)	0.221	0.89 (0.59-1.36)	0.6
ECOG PS (1 vs 0)	0.94 (0.68-1.29)	0.688	1.32 (0.87-1.98)	0.191
Cirrhosis (present vs absent)	1.4 (0.89-2.2)	0.14	1.23 (0.67-2.26)	0.504
Resection (yes vs no)	0.68 (0.44-1.06)	0.093	0.86 (0.5-1.46)	0.568
TACE (yes vs no)	0.8 (0.51-1.27)	0.352	0.24 (0.14-0.41)	< 0.001
Ablation (yes vs no)	0.83 (0.61-1.14)	0.259	0.71 (0.47-1.09)	0.116
Treatment line (later vs first)	0.66 (0.45-0.96)	0.032	0.82 (0.52-1.31)	0.404
Number (≥ 3 vs < 3)	1.46 (1.06-2.02)	0.021	1.84 (1.16-2.91)	0.009
Size (≥ 5 cm vs < 5 cm)	1.21 (0.87-1.68)	0.247	1.19 (0.78-1.83)	0.417
PVTT (present vs absent)	1.34 (0.98-1.83)	0.064	1.4 (0.92-2.11)	0.114
EHM (present vs absent)	1.12 (0.82-1.53)	0.472	1.52 (1-2.31)	0.047
Child-Pugh grade (B vs A)	0.97 (0.7-1.35)	0.849	1.37 (0.91-2.08)	0.135
BCLC stage (C vs B)	0.98 (0.65-1.48)	0.933	0.75 (0.44-1.25)	0.265

PFS: Progression-free survival; HR: Hazard ratio; OS: Overall survival; ECOG PS: Eastern Cooperative Oncology Group performance status; TACE: Transarterial chemoembolization; PVTT: Portal vein tumor thrombosis; EHM: Extrahepatic metastasis; BCLC: Barcelona Clinic Liver Cancer.