Clinical Outcomes By Child-Pugh Class in Patients With Advanced Hepatocellular Carcinoma in a Community Oncology Setting

Figures & data

Table 1. Demographic and clinical characteristics for patients with HCC stratified by Child-Pugh class at initial diagnosis.

Variable	Overall, n (%)	Child-Pugh class at initial diagnosis				p-value
		Class A, n (%)	Class B, n (%)	Class C, n (%)	Unknown, n (%)
Total patient count	352	150 (42.6)	127 (36.1)	33 (9.4)	42 (11.9)
Age at diagnosis (years)						0.0032
Patients with available data	352	150	127	33	42
Mean (SD), years	64.9 (10.4)	66.3 (10.1)	63.7 (10.1)	61.3 (11.0)	66.9 (10.8)
Median (Min, Max), years	64.0 (22.0, 91.3)	65.8 (33.6, 90.2)	62.6 (33.2, 91.3)	58.9 (43.8, 87.9)	66.8 (22.0, 85.4)
Age group						0.0216
<65Âyears	184 (52.3)	67 (44.7)	77 (60.6)	23 (69.7)	17 (40.5)
>75Âyears	62 (17.6)	28 (18.7)	21 (16.5)	4 (12.1)	9 (21.4)
≥65–75Âyears	106 (30.1)	55 (36.7)	29 (22.8)	6 (18.2)	16 (38.1)
Sex						0.3061
Female	80 (22.7)	39 (26.0)	26 (20.5)	5 (15.2)	10 (23.8)
Male	272 (77.3)	111 (74.0)	101 (79.5)	28 (84.8)	32 (76.2)
Race						0.8755
White	222 (63.1)	87 (58.0)	82 (64.6)	24 (72.7)	29 (69.0)
Black or African–American	29 (8.2)	12 (8.0)	12 (9.4)	2 (6.1)	3 (7.1)
Unknown	101 (28.7)	51 (34.0)	33 (26.0)	7 (21.2)	10 (23.8)
Ethnicity						0.0263
Hispanic or Latino	78 (22.2)	25 (16.7)	33 (26.0)	11 (33.3)	9 (21.4)
Not Hispanic or Latino	195 (55.4)	96 (64.0)	61 (48.0)	17 (51.5)	21 (50.0)
Unknown	79 (22.4)	29 (19.3)	33 (26.0)	5 (15.2)	12 (28.6)
Practice region						0.4023
South	254 (72.2)	97 (64.7)	95 (74.8)	25 (75.8)	37 (88.1)
West	51 (14.5)	27 (18.0)	14 (11.0)	6 (18.2)	4 (9.5)
Midwest	33 (9.4)	18 (12.0)	13 (10.2)	1 (3.0)	1 (2.4)
Northeast	14 (4.0)	8 (5.3)	5 (3.9)	1 (3.0)	0
Stage at initial diagnosis						0.5841
I	26 (7.4)	11 (7.3)	10 (7.9)	1 (3.0)	4 (9.5)
II	44 (12.5)	14 (9.3)	18 (14.2)	6 (18.2)	6 (14.3)
IIIA	48 (13.6)	23 (15.3)	11 (8.7)	9 (27.3)	5 (11.9)
IIIB	28 (8.0)	8 (5.3)	11 (8.7)	3 (9.1)	6 (14.3)
IIIC	6 (1.7)	2 (1.3)	1 (0.8)	1 (3.0)	2 (4.8)
IV	32 (9.1)	14 (9.3)	13 (10.2)	3 (9.1)	2 (4.8)
IVA	29 (8.2)	12 (8.0)	11 (8.7)	3 (9.1)	3 (7.1)
IVB	40 (11.4)	18 (12.0)	16 (12.6)	2 (6.1)	4 (9.5)
Unknown	99 (28.1)	48 (32.0)	36 (28.3)	5 (15.2)	10 (23.8)
ECOG						0.0020
0	39 (11.1)	23 (15.3)	12 (9.4)	0	4 (9.5)
1	208 (59.1)	94 (62.7)	69 (54.3)	19 (57.6)	26 (61.9)
2	53 (15.1)	16 (10.7)	25 (19.7)	5 (15.2)	7 (16.7)
3+	12 (3.4)	2 (1.3)	3 (2.4)	5 (15.2)	2 (4.8)
Not documented	40 (11.4)	15 (10.0)	18 (14.2)	4 (12.1)	3 (7.1)
Metastatic status						1.0000
No	302 (85.8)	128 (85.3)	109 (85.8)	29 (87.9)	36 (85.7)
Yes	50 (14.2)	22 (14.7)	18 (14.2)	4 (12.1)	6 (14.3)
Cirrhosis						0.0002
Yes	252 (71.6)	95 (63.3)	105 (82.7)	29 (87.9)	23 (54.8)
Not documented	100 (28.4)	55 (36.7)	22 (17.3)	4 (12.1)	19 (45.2)
Hepatitis B						0.0414
Yes	35 (9.9)	21 (14.0)	11 (8.7)	0	3 (7.1)
Not documented	317 (90.1)	129 (86.0)	116 (91.3)	33 (100)	39 (92.9)
Hepatitis C						0.0795
Yes	165 (46.9)	63 (42.0)	66 (52.0)	20 (60.6)	16 (38.1)
Not documented	187 (53.1)	87 (58.0)	61 (48.0)	13 (39.4)	26 (61.9)
Encephalopathy						<0.0001
None/absent	285 (81.0)	141 (94.0)	93 (73.2)	13 (39.4)	38 (90.5)
Mild/moderate	60 (17.0)	8 (5.3)	32 (25.2)	16 (48.5)	4 (9.5)
Severe	7 (2.0)	1 (0.7)	2 (1.6)	4 (12.1)	0
Ascites						<0.0001
None/absent	168 (47.7)	109 (72.7)	31 (24.4)	3 (9.1)	25 (59.5)
Mild/slight	123 (34.9)	34 (22.7)	65 (51.2)	11 (33.3)	13 (31.0)
Moderate/severe	61 (17.3)	7 (4.7)	31 (24.4)	19 (57.6)	4 (9.5)
Non-alcoholic fatty liver disease/steatohepatitis
Not documented	352 (100)	150 (100)	127 (100)	33 (100)	42 (100)
Cholangitis (acute)
Not documented	352 (100)	150 (100)	127 (100)	33 (100)	42 (100)
Barcelona Clinic Liver Cancer stage						<0.0001
A	11 (3.1)	7 (4.7)	4 (3.2)	0	0
B	15 (4.3)	9 (6.0)	6 (4.7)	0	0
C	224 (63.6)	119 (79.3)	105 (82.7)	0	0
D	40 (11.4)	2 (1.3)	3 (2.4)	33 (100)	2 (4.8)
Unknown	62 (17.6)	13 (8.7)	9 (7.1)	0	40 (95.2)
Presence of portal vein invasion/tumor thrombosis						0.9301
No	57 (16.2)	24 (16.0)	22 (17.3)	5 (15.2)	6 (14.3)
Yes	137 (38.9)	57 (38.0)	51 (40.2)	15 (45.5)	14 (33.3)
Not documented	158 (44.9)	69 (46.0)	54 (42.5)	13 (39.4)	22 (52.4)
Albumin (g/dl)						<0.0001
Patients with available data	352	150	127	33	42
Mean (SD)	3.3 (0.7)	3.6 (0.5)	3.0 (0.6)	2.7 (0.7)	3.5 (0.6)
Median (Min, Max)	3.3 (0.8, 5.0)	3.6 (2.3, 5.0)	3.1 (0.8, 4.6)	2.6 (1.8, 4.3)	3.6 (1.8, 4.7)
Prothrombin time (s)						<0.0001
Patients with available data	254	128	98	25	3
Mean (SD)	14.0 (4.1)	13.1 (3.5)	14.3 (4.1)	17.3 (5.7)	15.2 (1.0)
Median (Min, Max)	13.2 (7.2, 38.5)	12.5 (7.2, 38.5)	13.2 (8.9, 36.7)	15.4 (10.4, 32.0)	15.2 (14.3, 16.2)
INR						<0.0001
Patients with available data	281	145	109	27	0
Mean (SD)	1.2 (0.3)	1.1 (0.2)	1.3 (0.4)	1.5 (0.6)	. (.)
Median (min, max)	1.1 (0.8, 4.7)	1.1 (0.8, 2.2)	1.2 (0.9, 4.7)	1.4 (0.9, 3.0)	. (.,.)
Bilirubin (mg/dl)						<0.0001
Patients with available data	351	150	127	33	41
Mean (SD)	1.4 (1.4)	1.0 (1.0)	1.7 (1.5)	2.6 (2.0)	0.8 (0.4)
Median (Min, Max)	1.0 (0.1, 11.1)	0.8 (0.2, 11.1)	1.3 (0.1, 9.8)	2.1 (0.5, 7.5)	0.7 (0.2, 2.1)
Alpha-fetoprotein (ng/dl)						0.5288
Patients with available data	341	147	124	30	40
Mean (SD)	17270.7 (129980.7)	21796.6 (162577.5)	8307.6 (39301.5)	9299.3 (30821.3)	34402.1 (205135.9)
Median (Min, Max)	167.0 (0.7, 1935166)	110.0 (0.7, 1935166)	184.1 (2.4, 391800.0)	136.5 (1.1, 156040.0)	209.0 (1.0, 1299000)
Number of liver nodes						0.3611
Patients with available data	328	140	117	31	40
Mean (SD)	1.9 (1.6)	1.9 (1.6)	2.0 (1.5)	1.7 (1.2)	2.2 (2.1)
Median (Min, Max)	1.0 (1.0, 13.0)	1.0 (1.0, 10.0)	2.0 (1.0, 13.0)	1.0 (1.0, 5.0)	1.0 (1.0, 10.0)

ECOG: Eastern Cooperative Oncology Group; HCC: Hepatocellular carcinoma; INR: International normalized ratio; SD: Standard deviation.

Table 2. Most common first-line to second-line treatment sequences for patients with hepatocellular carcinoma.

1L regimen	2L regimen	HCC patients (n = 72), n (%)
Sorafenib	Nivolumab	27 (37.5)
Sorafenib	Regorafenib	17 (23.6)
Sorafenib	Capecitabine	5 (6.9)
Sorafenib	GemcitabineÂ+Âoxaliplatin	3 (4.2)
Sorafenib	Pembrolizumab	3 (4.2)
Sorafenib	Doxorubicin	2 (2.8)
Sorafenib	SorafenibÂ+Âdoxorubicin	2 (2.8)
Bevacizumab	GemcitabineÂ+Âoxaliplatin	1 (1.4)
CarboplatinÂ+Âetoposide	Etoposide	1 (1.4)
Doxorubicin	Gemcitabine	1 (1.4)

1L: First-line; 2L: Second-line; HCC: Hepatocellular carcinoma.

Table 3. Treatment characteristics of patients with hepatocellular carcinoma, stratified by Child-Pugh class at initial diagnosis.

Variable	Overall, n (%)	Child-Pugh class at initial diagnosis
		Class A, n (%)	Class B, n (%)	Class C, n (%)	Unknown, n (%)
Treatments prior to diagnosis
Total patient count	352	150	127	33	42
Liver transplantation	1 (100)	1 (100)	0	0	0
Number of prior non-systemic treatments for HCC
Patients with available data	4	2	1	0	1
Mean (SD)	1.0 (0.0)	1.0 (0.0)	1.0 (.)	–	1.0 (.)
Median (Min, Max)	1.0 (1.0, 1.0)	1.0 (1.0, 1.0)	1.0 (1.0, 1.0)	–	1.0 (1.0, 1.0)
TACE or TACE with drug eluting beads - doxorubicin	1 (0.3)	0	0	0	1 (2.4)
Radioembolization	2 (0.6)	1 (0.7)	1 (0.8)	0	0
Other therapy	1 (0.3)	1 (0.7)	0	0	0
Treatments prior to 1L initiation
Total patient count	352	150	127	33	42
Surgical resection	23 (100)	12 (100)	5 (100)	1 (100)	5 (100)
Liver transplantation	6 (100)	4 (100)	2 (100)	0	0
Number of prior liver-targeted treatments for HCC
Patients with available data	119	59	38	9	13
Mean (SD)	1.7 (0.9)	1.8 (1.0)	1.7 (0.8)	2.1 (1.4)	1.3 (0.9)
Median (Min, Max)	1.0 (1.0, 5.0)	1.0 (1.0, 5.0)	2.0 (1.0, 4.0)	2.0 (1.0, 5.0)	1.0 (1.0, 4.0)
Radiofrequency ablation	19 (5.4)	10 (6.7)	4 (3.2)	2 (6.1)	3 (7.1)
Microwave	6 (1.7)	2 (1.3)	4 (3.2)	0	0
Transarterial embolization	4 (1.1)	1 (0.7)	3 (2.4)	0	0
TACE or TACE with drug eluting beads - doxorubicin	72 (20.5)	31 (20.7)	26 (20.5)	8 (24.2)	7 (16.7)
Radioembolization	35 (9.9)	21 (14.0)	10 (7.9)	1 (3.0)	3 (7.1)
Other Therapy	10 (2.8)	7 (4.7)	2 (1.6)	1 (3.0)	0

1L: First-line; HCC: Hepatocellular carcinoma; SD: Standard deviation; TACE: Transcatheter arterial chemoembolization.

Table 4. Reasons for discontinuation of first-line treatment among patients with hepatocellular carcinoma.

Reasons for 1L treatment discontinuation	Overall (n = 352), n (%)	Child-Pugh (CP) risk score at 1L initiation
		Class A (n = 84), n (%)	Class B (n = 118), n (%)	Class C (n = 34), n (%)	Unknown (n = 116), n (%)
Progression	152 (43.2)	40 (47.6)	52 (44.1)	8 (23.5)	52 (44.8)
Toxicity	64 (18.2)	17 (20.2)	17 (14.4)	9 (26.5)	21 (18.1)
Death	28 (8.0)	3 (3.6)	9 (7.6)	6 (17.6)	10 (8.6)
Decline in performance status	13 (3.7)	3 (3.6)	7 (5.9)	1 (2.9)	2 (1.7)
Patient preference	5 (1.4)	3 (3.6)	1 (0.8)	0	1 (0.9)
Physician preference	4 (1.1)	1 (1.2)	1 (0.8)	1 (2.9)	1 (0.9)
Financial/insurance	3 (0.9)	0	0	0	3 (2.6)
Other	57 (16.2)	10 (11.9)	24 (20.3)	8 (23.5)	15 (12.9)
Not documented	2 (0.6)	1 (1.2)	1 (0.8)	0	0
Ongoing	24 (6.8)	6 (7.1)	6 (5.1)	1 (2.9)	11 (9.5)
Patients entering hospice care after 1L discontinuation but no 2L	124 (48.4)	21 (35.0)	42 (45.7)	12 (42.9)	49 (64.5)

1L: First-line; 2L: Second-line; HCC: Hepatocellular carcinoma.

Figure 1. Kaplan-Meier estimates: time to next treatment (A) and time to treatment failure (B) from initiation of 1L treatment stratified by Child-Pugh Class at initial diagnosis.

CI: Confidence interval; SE: Standard error; TTF: Time to treatment failure; TTNT: Time to next treatment.

Table 5. Response to first-line treatment for patients stratified by Child-Pugh class at first line initiation.

Best overall response to 1L treatment (physician assessed)	Overall, n (%)	Child-Pugh class at 1L initiation
		Class A, n (%)	Class B, n (%)	Class C, n (%)	Unknown, n (%)	p-value
Complete response	14 (4.0)	2 (2.4)	2 (1.7)	1 (2.9)	9 (7.8)
Response not otherwise specified	77 (21.9)	17 (20.2)	24 (20.3)	7 (20.6)	29 (25.0)
Stable disease	31 (8.8)	9 (10.7)	6 (5.1)	1 (2.9)	15 (12.9)
Mixed response	6 (1.7)	1 (1.2)	1 (0.8)	0	4 (3.4)
Progressive disease	130 (36.9)	38 (45.2)	45 (38.1)	7 (20.6)	40 (34.5)
Not evaluated	94 (26.7)	17 (20.2)	40 (33.9)	18 (52.9)	19 (16.4)

1L: First-line.

Figure 2. Overall survival from 1L treatment initiation stratified by Child-Pugh Class at initial diagnosis (A) overall (B) among patients with prior liver-targeted treatments and (C) without prior liver-targeted treatments.

CI: Confidence interval; CP: Child-Pugh; SE: Standard error.

Figure 3. Progression-free survival from 1L treatment initiation stratified by Child-Pugh Class at initial diagnosis (A) overall (B) among patients with prior liver-targeted treatments and (C) without prior liver-targeted treatments.

CI: Confidence interval; CP: Child-Pugh; PFS: Progression-free survival; SE: Standard error.