The benefit of Avastin re-treatment in metastatic colorectal cancer patients who were exposed to Avastin in previous therapies has not been addressed in randomized clinical trials.

Metastatic breast cancer (mBC)

Two large Phase III trials were designed to investigate the treatment effect of Avastin in combination with two individual chemotherapy agents, as measured by the primary endpoint of PFS. A clinically meaningful and statistically significant improvement in PFS was observed in both trials.

Summarised below are PFS results for the individual chemotherapy agents included in the indication:

• Study E2100 (paclitaxel)

• Median PFS increase 5.6 months, HR 0.421 (p <0.0001, 95% CI 0.343 ; 0.516)

• Study AVF3694g (capecitabine)

• Median PFS increase 2.9 months, HR 0.69 (p = 0.0002, 95% CI 0.56 ; 0.84)

Further details of each study and the results are provided below.

ECOG E2100

Trial E2100 was an open-label, randomised, active controlled, multicentre clinical trial eva luating Avastin in combination with paclitaxel for locally recurrent or metastatic breast cancer in patients who had not previously received chemotherapy for locally recurrent and metastatic disease. Patients were randomised to paclitaxel alone (90 mg/m2 IV over 1 hour once weekly for three out of four weeks) or in combination with Avastin (10 mg/kg IV infusion every two weeks). Prior hormonal therapy for the treatment of metastatic disease was allowed. Adjuvant taxane therapy was allowed only if it was completed at least 12 months prior to trial entry. Of the 722 patients in the trial, the majority of patients had HER2-negative disease (90%), with a small number of patients with unknown (8%) or confirmed HER2-positive status (2%), who had previously been treated with or were considered unsuitable for trastuzumab therapy. Furthermore, 65% of patients had received adjuvant chemotherapy including 19% prior taxanes and 49% prior anthracyclines. Patients with central nervous system metastasis, including previously treated or resected brain lesions, were excluded.

In trial 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 8.
Table 8 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