(p=0.0026)
 6.5

(p=0.0301)
 
Hazard ratio
   0.75

[0.62; 0.91]
 0.82

[0.68; 0.98]
 
Best overall response ratea
 20.1%
 34.1%

(p < 0.0001)
 30.4%

(p=0.0023)
 

a patients with measurable disease at baseline

Overall survival
 
Median (months)
 13.1
 13.6

(p=0.4203)
 13.4

(p=0.7613)
 
Hazard ratio
   0.93

[0.78; 1.11]
 1.03

[0.86, 1.23]
 

Advanced and/or metastatic renal cell cancer (mRCC)

Avastin in combination with interferon alfa-2a for the first-line treatment of advanced and/ or metastatic renal cell cancer (BO17705)

This was a phase III randomised double-blind trial conducted to eva luate the efficacy and safety of Avastin in combination with interferon (IFN) alfa-2a versus IFN alfa-2a alone as first-line treatment in mRCC. The 649 randomised patients (641 treated) had Karnofsky Performance Status (KPS) of ≥ 70%, no CNS metastases and adequate organ function. Patients were nephrectomised for primary renal cell carcinoma. Avastin 10 mg/kg was given every 2 weeks until disease progression. IFN alfa-2a was given up to 52 weeks or until disease progression at a recommended starting dose of 9 MIU three times a week, allowing a dose reduction to 3 MIU three times a week in 2 steps. Patients were stratified according to country and Motzer score and the treatment arms were shown to be well balanced for the prognostic factors.

The primary endpoint was overall survival, with secondary endpoints for the trial including progression-free survival. The addition of Avastin to IFN-alpha-2a significantly increased PFS and objective tumour response rate. These results have been confirmed through an independent radiological review. However, the increase in the primary endpoint of overall survival by 2 months was not significant (HR= 0.91). A high proportion of patients (approximately 63% IFN/placebo; 55% Avastin/IFN) received a variety of non-specified post-trial anti-cancer therapies, including antineoplastic agents, which may have impacted the analysis of overall survival.

The efficacy results are presented in Table 14.

Table 14 Efficacy results for trial BO17705

  BO17705
 
Placebo + IFNa
 Bvb + IFNa
 
Number of patients
 322
 327
 
Progression-free survival
    
Median (months)
 5.4
 10.2
 
Hazard ratio

95% CI
 0.63

0.52, 0.75

(p-value < 0.0001)
 
Objective response rate (%) in Patients with measurable disease
    
N
 289
 306
 
Response rate
 12.8%
 31.4%
 
  (p-value < 0.0001)
 

a Interferon alfa-2a 9 MIU 3x/week

b Bevacizumab 10 mg/kg q 2 wk

Overall survival
    
Median (months)
 21.3
 23.3
 
Hazard ratio

95% CI
 0.91

0.76, 1.10

(p-value 0.3360)
 

An exploratory multivariate Cox regression model using backward selection indicated that the following baseline prognostic factors were strongly associated with survival