Table 2.

Prognostic factor analysis for progression-free survival (PFS) and overall survival (OS) in the overall population

Variable	Category	Univariate Cox regression for PFS		Multivariate Cox regression for PFS		Univariate Cox regression for OS		Multivariate Cox regression for OS
		HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P
Age		1.00 (0.99-1.01)	0.756			1.01 (1.00-1.02)	0.007	1.01 (1.00-1.02)	0.003
Sex	Female	Reference		Reference		Reference
	Male	0.86 (0.73-1.02)	0.086	0.95 (0.80-1.13)	0.561	0.99 (0.84-1.17)	0.939
ECOG performance status	0	Reference				Reference		Reference
	$\ge$ 1	1.12 (0.94-1.33)	0.198			1.19 (1.01-1.40)	0.038	1.06 (0.90-1.25)	0.503
Any viral hepatitis B	No	Reference				Reference
	Yes	0.88 (0.71-1.10)	0.269			0.90 (0.73-1.11)	0.336
Any viral hepatitis C	No	Reference				Reference
	Yes	1.01 (0.38-2.71)	0.980			1.23 (0.46-3.30)	0.677
Level of carbohydrate antigen 19-9	Normal	Reference		Reference		Reference		Reference
	Elevated	1.46 (1.22-1.75)	<0.001	1.50 (1.25-1.80)	<0.001	1.71 (1.43-2.03)	<0.001	1.66 (1.39-1.98)	<0.001
Primary tumor location	Intrahepatic	Reference		Reference		Reference
	Extrahepatic	1.01 (0.84-1.23)	0.889	1.08 (0.88-1.33)	0.469	1.13 (0.94-1.35)	0.197
	Gall-bladder	1.35 (1.09-1.67)	0.006	1.41 (1.14-1.76)	0.002	1.02 (0.83-1.26)	0.839
Tumor histological type	Adenocarcinoma	Reference		Reference		Reference		Reference
	Adenosquamous carcinoma	2.34 (1.32-4.15)	0.004	2.08 (1.15-3.77)	0.016	2.03 (1.12-3.68)	0.020	2.54 (1.37-4.70)	0.003
Degree of differentiation	Well	Reference		Reference		Reference		Reference
	Moderately	1.52 (1.10-2.09)	0.011	1.48 (1.06-2.05)	0.020	1.17 (0.87-1.58)	0.289	1.06 (0.78-1.43)	0.716
	Poorly or undifferentiated	1.94 (1.39-2.71)	<0.001	1.69 (1.19-2.40)	0.003	1.34 (0.98-1.83)	0.068	1.10 (0.80-1.52)	0.554
Disease status	Locally advanced	Reference		Reference		Reference		Reference
	Initially metastatic	1.96 (1.46-2.64)	<0.001	1.50 (1.09-2.07)	0.012	1.76 (1.36-2.28)	<0.001	1.60 (1.21-2.12)	0.001
	Recurrent after curative-intent surgery	1.58 (1.17-2.14)	0.003	1.48 (1.08-2.04)	0.014	1.25 (0.96-1.63)	0.099	1.21 (0.92-1.60)	0.178
Liver metastasis	No	Reference		Reference		Reference		Reference
	Yes	1.69 (1.43-2.00)	<0.001	1.49 (1.24-1.78)	<0.001	1.54 (1.31-1.81)	<0.001	1.35 (1.14-1.61)	<0.001
MSI status	MSS	Reference				Reference		Reference
	MSI-H	1.62 (0.89-2.94)	0.116			0.45 (0.22-0.90)	0.024	0.44 (0.22-0.90)	0.024
First-line chemotherapy regimen	GemCis with ICIs	Reference				Reference
	GemCis with or without non-ICIs	1.11 (0.80-1.55)	0.538			1.30 (0.93-1.82)	0.120
MDM2-amp/TP53-WT status	No	Reference		Reference		Reference		Reference
	Yes	0.64 (0.43-0.96)	0.031	0.63 (0.42-0.94)	0.025	0.76 (0.52-1.10)	0.149	0.70 (0.48-1.02)	0.065

amp, amplification; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; GemCis, gemcitabine plus cisplatin; HR, hazard ratio; ICI, immune checkpoint inhibitor; MSI, microsatellite instability; MSI-H, microsatellite instability-high; MSS, microsatellite stable; WT, wild-type.