(n=699)
 P value
 
Primary endpoint
 
Median PFS**
 8.0
 9.4
 0.0023
 
Hazard ratio (97.5% CI)a
 0.83 (0.72–0.95)
  
Secondary endpoints
 
Median PFS (on treatment)**
 7.9
 10.4
 <0.0001
 
Hazard ratio (97.5% CI)
 0.63 (0.52-0.75)
  
Overall response rate

(invest. assessment)**
 49.2%,
 46.5%
  
Median overall survival*
 19.9
 21.2
 0.0769
 
Hazard ratio (97.5% CI)
 0.89 (0.76-1.03)

* Overall survival analysis at clinical cut-off 31 January 2007

** Primary analysis at clinical cut-off 31 January 2006

a relative to control arm

In the FOLFOX treatment subgroup, the median PFS was 8.6 months in placebo and 9.4 months in bevacizumab treated patients, HR = 0.89, 97.5% CI = [0.73 ; 1.08]; p-value = 0.1871, the corresponding results in the XELOX treatment subgroup being 7.4 vs. 9.3 months, HR = 0.77, 97.5% CI = [0.63 ; 0.94]; p-value = 0.0026.

The median overall survival was 20.3 months in placebo and 21.2 months in bevacizumab treated patients in the FOLFOX treatment subgroup, HR=0.94, 97.5% CI = [0.75 ; 1.16]; p-value = 0.4937, the corresponding results in the XELOX, treatment subgroup being 19.2 vs. 21.4 months, HR = 0.84, 97.5% CI = [0.68 ; 1.04]; p-value = 0.0698.

ECOG E3200

This was a phase III randomised, active-controlled, open-label trial investigating Avastin 10 mg/kg in combination with leucovorin with 5-fluorouracil bolus and then 5-fluorouracil infusional, with IV oxaliplatin (FOLFOX-4), administered on a 2-weekly schedule in previously-treated patients (second line) with advanced colorectal cancer. In the chemotherapy arms, the FOLFOX-4 regimen used the same doses and schedule as shown in Table 5 for trial NO16966.

The primary efficacy parameter of the trial was overall survival, defined as the time from randomization to death from any cause. Eight hundred and twenty-nine patients were randomised (292 FOLFOX-4, 293 Avastin + FOLFOX-4 and 244 Avastin monotherapy). The addition of Avastin to FOLFOX-4 resulted in a statistically significant prolongation of survival. Statistically significant improvements in progression-free survival and objective response rate were also observed (see Table 7).

Table 7 Efficacy results for trial E3200

  E3200
 
  FOLFOX-4
 FOLFOX-4 + Avastina
 
Number of patients
 292
 293
 
Overall survival
 
Median (months)
 10.8
 13.0
 
95% confidence interval
 10.12 – 11.86
 12.09 – 14.03
 
Hazard ratiob
 0.751

(p-value = 0.0012)
 
Progression-free survival
 
Median (months)
 4.5
 7.5
 
Hazard ratio
 0.518

(p-value < 0.0001)
 
Objective response rate
 
Rate
 8.6%
 22.2%
 
(p-value <0.0001)
 
a 10 mg/kg every 2 weeks

b Relative to control arm
 
No significant difference was observed in the duration of overall survival between patients who received Avastin monotherapy compared to patients treated with FOLFOX-4. Progre