AVF2192g
This was a phase II randomised, double-blind, active-controlled clinical trial eva luating the efficacy and safety of Avastin in combination with 5-FU/FA as first-line treatment for metastatic colorectal cancer in patients who were not optimal candidates for first-line irinotecan treatment. One hundred and five patients were randomised to 5-FU/FA + placebo arm and 104 patients to 5-FU/FA + Avastin (5 mg/kg every 2 weeks) arm. All treatments were continued until disease progression. The addition of Avastin 5 mg/kg every two weeks to 5-FU/FA resulted in higher objective response rates, significantly longer progression-free survival, and a trend in longer survival as compared to 5-FU/FA chemotherapy alone.
AVF0780g

This was a phase II randomised, active-controlled, open-labelled clinical trial investigating Avastin in combination with 5-FU/FA as first-line treatment of metastatic colorectal cancer. The median age was 64 years. 19% of the patients had received prior chemotherapy and 14% prior radiotherapy. Seventy-one patients were randomised to receive bolus 5-FU/FA or 5-FU/FA + Avastin (5 mg/kg every 2 weeks). A third group of 33 patients received bolus 5-FU/FA + Avastin (10 mg/kg every 2 weeks). Patients were treated until disease progression. The primary endpoints of the trial were objective response rate and progression-free survival. The addition of Avastin 5 mg/kg every two weeks to 5-FU/FA resulted in higher objective response rates, longer progression-free survival, and a trend in longer survival, compared with 5-FU/FA chemotherapy alone (see Table 4). These efficacy data are consistent with the results from trial AVF2107g.

The efficacy data from trials AVF0780g and AVF2192g investigating Avastin in combination with 5-FU/FA-chemotherapy are summarised in Table 4.

Table 4 Efficacy results for trials AVF0780g and AVF2192g

  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% Confidence interval
       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