The primary efficacy variable of the trial was overall survival. The addition of Avastin to IFL resulted in statistically significant increases in overall survival, progression-free survival and overall response rate (see Table 4). The clinical benefit, as measured by overall survival, was seen in all pre-specified patient subgroups, including those defined by age, sex, performance status, location of primary tumour, number of organs involved and duration of metastatic disease.

The efficacy results of Avastin in combination with IFL-chemotherapy are displayed in Table 4.

Table 4 Efficacy results for trial AVF2107g

  AVF2107g
 
Arm 1

 IFL + placebo
 Arm 2

IFL + Avastina
 
Number of patients
 411
 402
 
Overall survival
 
Median time (months)
 15.6
 20.3
 
95% CI
 14.29 - 16.99
 18.46 - 24.18
 
Hazard ratiob
  0.660

(p-value = 0.00004)
 
Progression-free survival
 
Median time (months)
 6.2
 10.6
 
Hazard ratio
 0.54

(p-value < 0.0001)
 
Overall response rate
 
Rate (%)
 34.8
 44.8
 
  (p-value = 0.0036)
 

a 5 mg/kg every 2 weeks.

b Relative to control arm.

Among the 110 patients randomised to Arm 3 (5-FU/FA + Avastin) prior to discontinuation of this arm, the median overall survival was 18.3 months and the median progression free survival was 8.8 months.

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 5). 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 5.

Tabl