Table III. Biologic end points associated with clinical parameters.

Proof of mechanism endpoints	r value	p value
End point in tumor biopsies
Decreased p-ERK with sorafenib therapy versus bevacizumab single agents		0.02
Decreased CD31 count with bevacizumab therapy versus sorafenib single agents		0.05
Decreased pERK at 2 weeks with increased circulating VEGF levels at 2 weeksa	−0.60	0.024
Decreased pERK at 2 weeks with increased circulating VEGF levels at 6 weeks	−0.63	0.050
Dynamic imaging end points
Reduced PET activity in patients with PR or S.D. > 4 cycles versus PD		0.047
Increased vascular perfusion (Ktrans) on DCE-MRIa at 2 weeks with increased VEGF in tumor biopsies at 6 weeks	0.72	0.042
Increased vascular permeability (Kep) on DCE-MRI at 6 weeks with increased tumor CD31 at 2 weeksa	0.75	0.02
Increased vascular permeability (Kep) with sorafenib treatment, first versus later		0.01
Decreased PET activity at 6 weeks with PR or S.D. versus PD		0.047
Biological end points associated with disease behavior
Decreased p-ERK in tumor with regression/necrosis in post-treatment biopsy		0.011
Decreased p-AKT in tumor with regression/necrosis in post-treatment biopsy		0.015
Increased cleaved PARP with greater number of treatment cycles	0.59	0.0072
Increased cleaved caspase 3 at 6 weeks with increased number of cycles of therapy	0.50	0.030
Decreased Ki67 at 6 weeks with increased number of cycles of therapy	−0.70	0.016
Biologic end points associated with number of cycles of treatment
Lower cleaved PARP at base line	−0.45	0.053
Lower p-VEGFR2 at base line	−0.45	0.053
Decreased PET activity at 2 weeksa	−0.41	0.044

^a Two-week analyses were done with pooled data from both monotherapy groups to maintain analytic power.