AVF0780g
 AVF2192g
 
5-FU/FA
 5-FU/FA + Avastina
 5-FU/FA + Avastinb
  5-FU/FA + placebo
  5-FU/FA + Avastin
 
Number of patients
 36
 35
 33
 105
 104
 
Overall survival
 
Median time (months)
 13.6
 17.7
 15.2
 12.9
 16.6
 
95% CI
       10.35 - 16.95
 13.63 - 19.32
 
Hazard ratioc
  -
  0.52
  1.01
    0.79
 
p-value
   0.073
 0.978
   0.16
 
Progression-free survival
 
Median time (months)
 5.2
 9.0
 7.2
 5.5
 9.2
 
Hazard ratio
   0.44
 0.69
   0.5
 
p-value
 -
 0.0049
 0.217
   0.0002
 
Overall response rate
 
Rate (percent)
 16.7
 40.0
 24.2
 15.2
 26
 
95% CI
 7.0 − 33.5
 24.4 − 57.8
 11.7 - 42.6
 9.2 - 23.9
 18.1 - 35.6
 
p-value
   0.029
 0.43
   0.055
 
Duration of response
 
Median time (months)
 NR
 9.3
 5.0
 6.8
 9.2
 
25-75 percentile (months)
 5.5 − NR
 6.1 − NR
 3.8 - 7.8
 5.59 - 9.17
 5.88 - 13.01
 

a 5 mg/kg every 2 weeks.

b 10 mg/kg every 2 weeks.

c Relative to control arm.

NR = not reached.

NO16966

This was a phase III randomised, double-blind (for bevacizumab), clinical trial investigating Avastin 7.5 mg/kg in combination with oral capecitabine and IV oxaliplatin (XELOX), administered on a 3-weekly schedule; or Avastin 5 mg/kg in combination with leucovorin with 5-fluorouracil bolus, followed by 5-fluorouracil infusional, with IV oxaliplatin (FOLFOX-4), administered on a 2-weekly schedule. The trial contained two parts: an initial unblinded 2-arm part (Part I) in which patients were randomised to two different treatment groups (XELOX and FOLFOX-4) and a subsequent 2 x 2 factorial 4-arm part (Part II) in which patients were randomised to four treatment groups (XELOX + placebo, FOLFOX-4 + placebo, XELOX + Avastin, FOLFOX-4 + Avastin). In Part II, treatment assignment was double-blind with respect to Avastin.

Approximately 350 patients were randomised into each of the 4 trial arms in the Part II of the trial.

Table 6 Treatment regimens in trial NO16966 (mCRC)

  Treatment
 Starting dose
 Schedule
 
FOLFOX-4

or

FOLFOX-4 + Avastin
  Oxaliplatin
 85 mg/m2 IV 2 h
  Oxaliplatin on day 1
 
 Leucovorin
 200 mg/m2 IV 2 h
  Leucovorin on day 1 and 2
 
 5-Fluorouracil
 400 mg/m2 IV bolus, 600 mg/m2 IV 22 h
  5-fluorouracil IV bolus/infusion, each on days 1 and 2
 
Placebo or Avastin
 5 mg/kg IV 30-90 min
 Day 1, prior to FOLFOX-4, every 2 weeks
 
XELOX

or

XELOX + Avastin
  Oxaliplatin
 130 mg/