Statistical analyses were performed independently for 1) patients who received capecitabine in combination with Avastin or placebo; 2) patients who received taxane-based or anthracycline-based chemotherapy in combination with Avastin or placebo. The primary endpoint of the study was PFS by investigator assessment. In addition, the primary endpoint was also assessed by an independent review committee (IRC).

The results of this study from the final protocol defined analyses for progression free survival and response rates for the independently powered capecitabine cohort of Study AVF3694g are presented in Table 11 Results from an exploratory overall survival analysis which include an additional 7 months of follow-up (approximately 46% of patients had died) are also presented. The percentage of patients who received Avastin in the open-label phase was 62.1% in the capecitabine + placebo arm and 49.9% in the capecitabine + Avastin arm.

Table 11 Efficacy results for study AVF3694g: – Capecitabinea and Avastin/Placebo (Cap + Avastin/Pl)

Progression-free survivalb
 
  Investigator Assessment
 IRC Assessment
 
  Cap + Pl

(n=206)
 Cap + Avastin

(n=409)
 Cap + Pl

(n=206)
 Cap + Avastin

(n=409)
 
Median PFS (months)
 5.7
 8.6
 6.2
 9.8
 
Hazard ratio vs placebo arm (95% CI)
 0.69 (0.56; 0.84)
 0.68 (0.54; 0.86)
 
p-value
 0.0002
 0.0011
 
Response rate (for patients with measurable disease)b
 
  Cap + Pl (n=161)
 Cap + Avastin (n=325)
 
% pts with objective response
 23.6
 35.4
 
p-value
 0.0097
 
Overall survivalb
 
HR

(95% CI)
 0.88 (0.69; 1.13)
 
p-value (exploratory)
 0.33
 

a1000 mg/m2 oral twice daily for 14 days administered every 3 weeks

bStratified analysis included all progression and death events except those where non-protocol therapy (NPT) was initiated prior to documented progression; data from those patients were censored at the last tumour assessment prior to starting NPT.

An unstratified analysis of PFS (investigator assessed) was performed that did not censor for non-protocol therapy prior to disease progression. The results of these analyses were very similar to the primary PFS results.

Non-small cell lung cancer (NSCLC)

The safety and efficacy of Avastin, in addition to platinum-based chemotherapy, in the first-line treatment of patients with non-squamous non-small cell lung cancer (NSCLC), was investigated in trials E4599 and BO17704. An overall survival benefit has been demonstrated in trial E4599 with a 15 mg/kg/q3wk dose of bevacizumab. Trial BO17704 has demonstrated that both 7.5 mg/kg/q3wk and 15 mg/kg/q3wk bevacizumab doses increase progression free survival and response rate.

E4599

E4599 was an open-label, randomised, active-controlled, multicentre clinical trial eva luating Avastin as first-line treatment of patients with locally advanced (stage IIIb with malignant pleural effusion), metastatic or recurrent NSCLC other than predominantly squamous cell histology.

Patients