Table 3.

Univariate and multivariable analysis of prognostic potential of biomarkers. Columns represent a univariate analysis in validation cohort followed by results when adjusting for risk in all patients and in each treatment arm separately. Univariate analysis of risk of progression in all patients and in each treatment arm separately is displayed in the fifth row of each cohort. HRs for biomarkers refer to increase in risk per unit increase in concentration.

			Univariate analysis		Multivariable analysis
					+adj for risk		+adjusted for risk (standard arm)		+adjusted for risk (experimental arm)
		Level	HR (95% CI)	p-value	HR (95% CI)	p-value	HR (95% CI)	p-value	HR (95% CI)	p-value
Validation cohort I
Mesothelin (nM)	Risk	(-)	1.08 (1.03,1.14)	0.002	1.08 (1.02,1.14)	0.005	1.04 (0.97,1.12)	0.23	1.30 (1.13,1.50)	<0.001
		Not high	(-)		1		1		1
		High	(-)		1.05 (0.61,1.8)	0.871	1.08 (0.51,2.28)	0.84	0.82 (0.37,1.82)	0.623
FLT4 (ng/mL)	Risk	(-)	1.02 (1.01,1.04)	0.008	1.02 (1.00,1.04)	0.011	1.02 (1.00,1.04)	0.063	1.02 (1.00,1.05)	0.102
		Not high	(-)		1		1		1
		High	(-)		1.14 (0.69,1.90)	0.602	1.17 (0.58,2.38)	0.663	1.14 (0.54,2.42)	0.726
AGP (g/L)	Risk	(-)	2.29 (1.40,3.75)	0.001	2.25 (1.37,3.69)	0.001	2.06 (1.04,4.08)	0.038	2.65 (1.21,5.82)	0.015
		Not high	(-)		1		1		1
		High	(-)		1.17 (0.71,1.95)	0.538	1.27 (0.62,2.59)	0.514	1.05 (0.48,2.27)	0.906
CA-125 (ku/L)	Risk	(-)	1.05 (1.03,1.08)	<0.001	1.05 (1.03,1.07)	<0.001	1.04 (1.01,1.08)	0.024	1.07 (1.03,1.11)	0.001
		Not high	(-)		1		1		1
		High	(-)		1.40 (0.85,2.31)	0.189	1.37 (0.67,2.82)	0.384	1.48 (0.70,3.13)	0.302
Risk		(-)	(-)		(-)		(-)		(-)
		Not high	1		(-)		1		1
		High	1.51 (0.92.2.48)	0.103	(-)		1.28 (0.64,2.61)	0.482	1.86 (0.92,3.76)	0.0842
Validation cohort II
Mesothelin	Risk	(-)	1.10 (1.07,1.14)	<0.001	1.06 (1.02,1.1)	0.002	1.01 (0.96,1.06)	0.663	1.06 (0.96,1.17)	0.216
		Not high	(-)		1		1		1
		High	(-)		3.30 (2.00,5.47)	<0.001	6.80 (2.69,17.22)	<0.001	2.69 (1.43,5.03)	0.002
FLT4	Risk	(-)	1.01 (1.00,1.02)	0.050	1.01 (0.99,1.02)	0.286	1.01 (0.99,1.03)	0.32	1.01 (0.99,1.03)	0.423
		Not high	(-)		1		1		1
		High	(-)		3.96 (2.47,6.33)	<0.001	7.51 (3.41,16.54)	<0.001	2.86 (1.57,5.22)	0.001
AGP	Risk	(-)	2.03 (1.44,2.86)	<0.001	1.44 (0.95,2.16)	0.083	1.67 (0.96,2.93)	0.071	1.33 (0.74,2.37)	0.341
		Not high	(-)		1		1		1
		High	(-)		3.48 (2.11,5.74)	<0.001	6.75 (3.04,14.99)	<0.001	2.61 (1.34,5.05)	0.005
CA-125	Risk	(-)	1.03 (1.01,1.04)	<0.001	1.02 (1.00,1.03)	0.028	1.00 (0.98,1.02)	0.792	1.06 (1.02,1.10)	0.001
		Not high	(-)		1		1		1
		High	(-)		3.81 (2.37,6.15)	<0.001	7.83 (3.46,17.68)	<0.001	2.54 (1.37,4.68)	0.003
Risk		(-)	(-)		(-)		(-)		(-)
		Not high	1		(-)		1		1
		High	4.11 (2.58,6.54)	<0.001	(-)		7.56 (3.47,16.5)	<0.001	3.03 (1.69,5.43)	<0.001
Validation cohorts I and II combined
Mesothelin	Risk	(-)	1.10 (1.07,1.13)	<0.001	1.07 (1.04,1.11)	<0.001	1.05 (1.02,1.09)	0.004	1.11 (1.03,1.21)	0.01
		Not high	(-)		1		1		1
		High	(-)		2.04 (1.42,2.91)	<0.001	2.10 (1.2,3.68)	0.009	2.00 (1.22,3.28)	0.006
FLT4	Risk	(-)	1.01 (1.00,1.02)	0.003	1.01 (1.00,1.02)	0.009	1.01 (1.00,1.03)	0.014	1.01 (1.00,1.02)	0.183
		Not high	(-)		1		1		1
		High	(-)		2.46 (1.77,3.44)	<0.001	2.98 (1.78,5)	<0.001	2.33 (1.48,3.68)	<0.001
AGP	Risk	(-)	2.16 (1.63,2.86)	<0.001	1.86 (1.38,2.51)	<0.001	2.12 (1.41,3.18)	<0.001	1.69 (1.08,2.65)	0.021
		Not high	(-)		1		1		1
		High	(-)		2.14 (1.52,3.02)	<0.001	2.68 (1.62,4.46)	<0.001	2.00 (1.23,3.26)	0.005
CA-125	Risk	(-)	1.03 (1.02,1.04)	<0.001	1.00 (1.00,1.00)	<0.001	1.01 (1.00,1.03)	0.045	1.05 (1.03,1.08)	<0.001
		Not high	(-)		1		1		1
		High	(-)		2.32 (1.65,3.26)	<0.001	2.53 (1.52,4.24)	<0.001	2.13 (1.34,3.37)	0.001
Risk		(-)	(-)		(-)		(-)		(-)
		Not high	1		(-)		1		1
		High	2.53 (1.81,3.52)	<0.001	(-)		2.69 (1.62,4.46)	<0.001	2.51 (1.61,3.91)	<0.001