Correlation between immune-related adverse events and long-term outcomes in pembrolizumab-treated patients with unresectable hepatocellular carcinoma: A retrospective study

Table 1 Clinical characteristics of 190 patients

Clinical characteristic	No. of patients
Age (yr), median (IQR)	51 (42-58)
Sex
Male, n (%)	154 (81.1)
Etiology
Hepatitis B	144 (75.8)
Hepatitis C	4 (2.1)
Hepatitis B & C	2 (1.1)
Non-hepatitis B, non-hepatitis C	40 (21.0)
ALT (U/L), median (IQR)	75 (51-254)
AST (U/L), median (IQR)	57 (47-302)
TBiL (μmol/L), median (IQR)	20.1 (11.2-31.2)
AFP (ng/mL), median (IQR)	205 (19.2-4692)
Child-Pugh class
A	146 (76.8)
B	44 (23.2)
Portal vein tumor thrombosis	131 (68.9)
Extrahepatic metastasis
Lung	64 (33.7)
Bone	31 (16.3)
Peritoneum	25 (13.1)
Multiple locations	15 (7.9)
BCLC stage
C	190 (100)
Tumor response
Complete response	0 (0)
Partial response	23 (12.1)
Stable disease	76 (40.0)
Progressive disease	91 (47.9)
Follow-up time, median (range)	748 (438-1146) d
TTP, median (95%CI)	98 (75-124) d
OS, median (95%CI)	376 (340-411) d

IQR: Interquartile range; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TBiL: Total bilirubin; AFP: Alpha fetoprotein; TTP: Time to progression; OS: Overall survival; BCLC: Barcelona Clinic Liver Cancer; CI: Confidence interval.

Table 2 Incidence of treatment-related adverse events

Adverse event	Any grade	Grade 3	Grade 4
Cutaneous toxic effects	25 (13.2)	3 (1.6)	2 (1.1)
Mucositis	8 (4.2)	2 (1.1)	1 (< 1)
Rash	7 (3.7)	1 (< 1)	1 (< 1)
Pruritus	10 (5.3)	2 (1.1)	0 (0)
Diarrhea	27 (14.2)	4 (2.1)	1 (< 1)
Elevated transaminases	35 (18.4)	10 (5.3)	2 (1.1)
Hypothyroidism	25 (13.2)	4 (2.1)	2 (1.1)
Myocarditis	3 (1.6)	1 (< 1)	2 (1.1)
Hypoadrenocorticism	5 (2.6)	1 (< 1)	0 (0)
Proteinuria	18 (9.5)	5 (2.6)	0 (0)
Overall incidence	138 (72.6)	12 (6.3)	7 (3.7)

Table 3 Univariate and multivariate analyses of prognostic factors for predicting overall survival and time to progression

Variable	Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value
OS
Child-Pugh, class B	1.446 (1.044-1.547)	0.039	1.321 (1.112-1.711)	0.021
AFP > 400 ng/mL	1.651 (1.351-1.782)	0.021	1.446 (0.875-1.836)	0.239
PIVKA > 40 mAU/mL	1.324 (1.023-1.472)	0.043	1.568 (0.411-1.687)	0.085
PVTT, yes	2.145 (1.897-3.587)	0.003	3.125 (3.015-3.568)	0.008
Extrahepatic metastasis, yes	1.784 (1.254-2.571)	0.013	2.871 (2.581-3.052)	0.028
Cutaneous toxic effects, yes	0.741 (0.654-0.968)	0.025	0.845 (0.425-1.751)	0.129
Hypothyroidism, yes	0.623 (0.487-0.912)	0.034	0.641 (0.489-0.901)	0.017
TTP
AFP > 400 ng/mL	1.757 (1.271-1.972)	0.023	1.872 (1.357-2.135)	0.017
PVTT, yes	2.595 (1.377-3.889)	0.003	2.472 (2.243-2.891)	0.008
Extrahepatic metastasis, yes	1.536 (1.296-1.765)	0.031	1.489 (1.246-1.574)	0.012
Cutaneous toxic effects, yes	0.874 (0.621-0.925)	0.036	0.785 (0.358-1.258)	0.157
Hypothyroidism, yes	0.741 (0.514-0.870)	0.024	0.613 (0.362-0.886)	0.018

AFP: Alpha fetalprotein; PIVKA: Protein induced by vitamin K absence or antagonist-II; OS: Overall survival; PVTT: Portal vein tumor thrombus; HR: Hazard rate; TTP: Time to progression; CI: Confidence interval.