Table III Biologic end points associated with clinical parameters
Proof of mechanism endpointsr valuep value
End point in tumor biopsies
    Decreased p-ERK with sorafenib therapy versus bevacizumab single agents0.02
    Decreased CD31 count with bevacizumab therapy versus sorafenib single agents0.05
    Decreased pERK at 2 weeks with increased circulating VEGF levels at 2 weeksa−0.600.024
    Decreased pERK at 2 weeks with increased circulating VEGF levels at 6 weeks−0.630.050
Dynamic imaging end points
    Reduced PET activity in patients with PR or S.D. > 4 cycles versus PD0.047
    Increased vascular perfusion (Ktrans) on DCE-MRIa at 2 weeks with increased VEGF in tumor biopsies at 6 weeks0.720.042
    Increased vascular permeability (Kep) on DCE-MRI at 6 weeks with increased tumor CD31 at 2 weeksa0.750.02
    Increased vascular permeability (Kep) with sorafenib treatment, first versus later0.01
    Decreased PET activity at 6 weeks with PR or S.D. versus PD0.047
Biological end points associated with disease behavior
    Decreased p-ERK in tumor with regression/necrosis in post-treatment biopsy0.011
    Decreased p-AKT in tumor with regression/necrosis in post-treatment biopsy0.015
    Increased cleaved PARP with greater number of treatment cycles0.590.0072
    Increased cleaved caspase 3 at 6 weeks with increased number of cycles of therapy0.500.030
    Decreased Ki67 at 6 weeks with increased number of cycles of therapy−0.700.016
Biologic end points associated with number of cycles of treatment
    Lower cleaved PARP at base line−0.450.053
    Lower p-VEGFR2 at base line−0.450.053
    Decreased PET activity at 2 weeksa−0.410.044
  • a Two-week analyses were done with pooled data from both monotherapy groups to maintain analytic power.