The primary efficacy parameter of the trial was overall survival, defined as the time from randomisation 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 8).

Table 8 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% CI
 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. Progression-free survival and objective response rate were inferior in the Avastin monotherapy arm compared to the FOLFOX-4 arm.

ML18147

This was a Phase III randomised, controlled, open-label trial investigating Avastin 5.0 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks in combination with fluoropyrimidine-based chemotherapy versus fluoropyrimidine-based chemotherapy alone in patients with mCRC who have progressed on a first-line bevacizumab-containing regimen.

Patients with histologically confirmed mCRC and disease progression were randomised 1:1 within 3 months after discontinuation of bevacizumab first-line therapy to receive fluoropyrimidine/oxaliplatin- or fluoropyrimidine/irinotecan-based chemotherapy (chemotherapy switched depending on first-line chemotherapy) with or without bevacizumab. Treatment was given until progressive disease or unacceptable toxicity. The primary outcome measure was overall survival defined as the time from randomisation until death from any cause.

A total of 820 patients were randomised. The addition of bevacizumab to fluoropyrimidine-based chemotherapy resulted in a statistically significant prolongation of survival in patients with mCRC who have progressed on a first-line bevacizumab-containing regimen (ITT = 819) (see Table 9).

Table 9 Efficacy Results for Study ML18147 (ITT population)

  ML18147
 
  fluoropyrimidine/irinotecan or fluoropyrimidine/oxaliplatin based chemotherapy
 fluoropyrimidine/irinotecan or fluoropyrimidine/oxaliplatin based chemotherapy + Avastina
 
Number of Patients
 410
 409
 
Overall Survival
  
Median (months)
 9.8
 11.2
 
Hazard ratio (95% confidence interval)
 0.81 (0.69, 0.9