E2100, patients were treated until disease progression. In situations where early discontinuation of chemotherapy was required, treatment with Avastin as a single agent continued until disease progression. The patient characteristics were similar across the trial arms. The primary endpoint of this trial was progression free survival (PFS), based on trial investigators' assessment of disease progression. In addition, an independent review of the primary endpoint was also conducted. The results of this trial are presented in Table 10.
Table 10 Trial E2100 efficacy results
Progression-free survival
Investigator assessment*
IRF assessment
Paclitaxel
(n=354)
Paclitaxel/Avastin
(n=368)
Paclitaxel
(n=354)
Paclitaxel/Avastin
(n=368)
Median PFS (months)
5.8
11.4
5.8
11.3
HR
(95% CI)
0.421
(0.343; 0.516)
0.483
(0.385; 0.607)
p-value
< 0.0001
< 0.0001
Response rates (for patients with measurable disease)
Investigator assessment
IRF assessment
Paclitaxel
(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 oestrogen 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 randomisation 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 medicinal product (Avastin or placebo) every 3 weeks until disease progression, treatment-limiting toxicity, or death. On documented disease progression, patients who entered t
