95% CI (0.56, 0.76)
 
Overall response rate
 
Rate (percent)
 12.9
 29.0 (p<0.0001)
 
In an exploratory analysis, the extent of Avastin benefit on overall survival was less pronounced in the subgroup of patients who did not have adenocarcinoma histology.

BO17704

Trial BO17704 was a randomised, double-blind phase III trial of Avastin in addition to cisplatin and gemcitabine versus placebo, cisplatin and gemcitabine in patients with locally advanced (stage IIIb with supraclavicular lymph node metastases or with malignant pleural or pericardial effusion), metastatic or recurrent non-squamous NSCLC, who had not received prior chemotherapy. The primary endpoint was progression free survival, secondary endpoints for the trial included the duration of overall survival.

Patients were randomised to platinum-based chemotherapy, cisplatin 80 mg/m2 i.v. infusion on day 1 and gemcitabine 1250 mg/m2 i.v. infusion on days 1 and 8 of every 3-week cycle for up to 6 cycles (CG) with placebo or CG with Avastin at a dose of 7.5 or 15 mg/kg IV infusion day 1 of every 3-week cycle. In the Avastin-containing arms, patients could receive Avastin as a single-agent every 3 weeks until disease progression or unacceptable toxicity. Trial results show that 94% (277 / 296) of eligible patients went on to receive single agent bevacizumab at cycle 7. A high proportion of patients (approximately 62%) went on to receive a variety of non-protocol specified anti-cancer therapies, which may have impacted the analysis of overall survival.

The efficacy results are presented in Table 11.

Table 11 Efficacy results for trial BO17704

  Cisplatin/Gemcitabine + placebo
 Cisplatin/Gemcitabine + Avastin

7.5 mg/kg q 3 weeks
 Cisplatin/Gemcitabine + Avastin

15 mg/kg q 3 weeks
 
Number of patients
 347
 345
 351
 
Progression-free survival
      
Median (months)
 6.1
 6.7

(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 rate a
 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 Advance 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 (Roferon®) versus IFN alfa-2a alone as first-line treatment in mRCC. The 649 randomized 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 un