(n=273)
 Paclitaxel/Avastin

(n=252)
 Paclitaxel

(n=243)
 Paclitaxel/Avastin

(n=229)
 
% pts with objective response
 23.4
 48.0
 22.2
 49.8
 
p-value
 <0.0001
 <0.0001

* primary analysis

Overall survival
 
 
 Paclitaxel

(n=354)
 Paclitaxel/Avastin

(n=368)
 
Median OS (months)
 24.8
 26.5
 
HR

(95% CI)
 0.869

(0.722 ; 1.046)
 
p-value
 0.1374
The clinical benefit of Avastin as measured by PFS was seen in all pre-specified subgroups tested (including disease-free interval, number of metastatic sites, prior receipt of adjuvant chemotherapy and estrogen receptor (ER) status).
AVF3694g
Study AVF3694g was a Phase III, multicentre, randomised, placebo-controlled trial designed to eva luate the efficacy and safety of Avastin in combination with chemotherapy compared to chemotherapy plus placebo as first-line treatment for patients with HER2-negative metastatic or locally recurrent breast cancer.

Chemotherapy was chosen at the investigator's discretion prior to randomization in a 2:1 ratio to receive either chemotherapy plus Avastin or chemotherapy plus placebo. The choices of chemotherapy included capecitabine, taxane (protein-bound paclitaxel, docetaxel), and anthracycline-based agents (doxorubicin/ cyclophosphamide, epirubicin/ cyclophosphamide, 5-fluorouracil/ doxorubicin/ cyclophosphamide, 5-fluorouracil/epirubicin/cyclophosphamide) given every three weeks (q3w). Avastin or placebo was administered at a dose of 15 mg/kg q3w.

This study included a blinded treatment phase, an optional open-label post-progression phase, and a survival follow-up phase. During the blinded treatment phase, patients received chemotherapy and study drug (Avastin or placebo) every 3 weeks until disease progression, treatment-limiting toxicity, or death. On documented disease progression, patients who entered the optional open-label phase could receive open-label Avastin together with a wide-range of second line therapies.
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 9. 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 9 Efficacy results for study AVF3694g: – Capecitabinea and Avastin/Placebo (Cap + Avastin/Pl)
Progression-free survivalb
 
  Investigator Assessment
 IRC Assessment
&