Avastin

4. E2100 Study Design: Randomized, double-blind, placebo-controlled, multicentre, phase III trial Primary end point: progression-free survival (PFS) Secondary end points: overall response rate, overall survival, quality of life E2100 is an ongoing open-label, phase III trial in which Bevacizumab is being evaluated in combination with weekly paclitaxel as first-line therapy for MBC.1 Patients recruited to this trial are less heavily pretreated than patients in AVF2119g. A total of 722 patients have been randomised to one of two arms: paclitaxel 90mg/m2 alone every week for 3 weeks followed by 1 week without treatment or paclitaxel plus Bevacizumab 10mg/kg every 2 weeks. No cross over is permitted in this trial. Objectives are to compare progression-free survival (PFS), overall response rate and overall survival (OS) between the arms. 1. Miller KD, Wang M, Gralow J, et al. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100). Breast Cancer Res Treat 2005;94:S6 (Abstract 3).E2100 is an ongoing open-label, phase III trial in which Bevacizumab is being evaluated in combination with weekly paclitaxel as first-line therapy for MBC.1 Patients recruited to this trial are less heavily pretreated than patients in AVF2119g. A total of 722 patients have been randomised to one of two arms: paclitaxel 90mg/m2 alone every week for 3 weeks followed by 1 week without treatment or paclitaxel plus Bevacizumab 10mg/kg every 2 weeks. No cross over is permitted in this trial. Objectives are to compare progression-free survival (PFS), overall response rate and overall survival (OS) between the arms. 1. Miller KD, Wang M, Gralow J, et al. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100). Breast Cancer Res Treat 2005;94:S6 (Abstract 3).

5. E2100 Trial: PFS Results The Kaplan-Meier curve shown here demonstrates the effect of Bevacizumab plus paclitaxel on PFS.1 A significant increase in median PFS was observed in patients receiving Bevacizumab plus paclitaxel compared with paclitaxel alone (11.4 months vs 6.11 months, respectively). The hazard ratio (HR) for progression was 0.51 (p<0.0001), which corresponds to a two-fold chance of being progression free. 1. Miller KD, Wang M, Gralow J, et al. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100). Breast Cancer Res Treat 2005;94:S6 (Abstract 3). The Kaplan-Meier curve shown here demonstrates the effect of Bevacizumab plus paclitaxel on PFS.1 A significant increase in median PFS was observed in patients receiving Bevacizumab plus paclitaxel compared with paclitaxel alone (11.4 months vs 6.11 months, respectively). The hazard ratio (HR) for progression was 0.51 (p<0.0001), which corresponds to a two-fold chance of being progression free. 1. Miller KD, Wang M, Gralow J, et al. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100). Breast Cancer Res Treat 2005;94:S6 (Abstract 3).

6. E2100 Trial: Overall Response Rate A significant, more than two-fold increase in overall response rate (complete response plus partial response) was observed in all patients receiving Bevacizumab plus paclitaxel compared with paclitaxel alone (29.9% vs 13.8%, p<0.0001).1 A significant increase in response rate was also seen in patients with measurable disease receiving Bevacizumab plus paclitaxel compared with those receiving paclitaxel alone (37.7% vs 16.0%, p<0.0001). 1. Miller KD, Wang M, Gralow J, et al. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100). Breast Cancer Res Treat 2005;94:S6 (Abstract 3).A significant, more than two-fold increase in overall response rate (complete response plus partial response) was observed in all patients receiving Bevacizumab plus paclitaxel compared with paclitaxel alone (29.9% vs 13.8%, p<0.0001).1 A significant increase in response rate was also seen in patients with measurable disease receiving Bevacizumab plus paclitaxel compared with those receiving paclitaxel alone (37.7% vs 16.0%, p<0.0001). 1. Miller KD, Wang M, Gralow J, et al. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100). Breast Cancer Res Treat 2005;94:S6 (Abstract 3).

7. AVADO Study Design: Randomized, double-blind, placebo-controlled, multicentre, phase III trial A randomised, double-blind, placebo-controlled, multicentre phase III trial commenced recruitment in late March 2006. A planned total of 705 patients will receive docetaxel at a dose of 100mg/m2 every three weeks with either placebo, Bevacizumab 7.5mg/kg or Bevacizumab 15mg/kg. The primary trial endpoint will be progression-free survival. Secondary endpoints will include overall response rate, duration of response, time to treatment failure, overall survival, safety and quality of life.A randomised, double-blind, placebo-controlled, multicentre phase III trial commenced recruitment in late March 2006. A planned total of 705 patients will receive docetaxel at a dose of 100mg/m2 every three weeks with either placebo, Bevacizumab 7.5mg/kg or Bevacizumab 15mg/kg. The primary trial endpoint will be progression-free survival. Secondary endpoints will include overall response rate, duration of response, time to treatment failure, overall survival, safety and quality of life.

11. Ongoing RIBBON 1 Phase IIITrial Study Design Further development of Bevacizumab in breast cancer is planned following the positive results of the US E2100 study. This phase III trial, to be conducted in countries worldwide, will investigate further combinations of Avastin and chemotherapy. The primary trial endpoint is progression-free survival. Investigators assign patients to a chemotherapy regimen, including specified regimens of anthracycline-based combination chemotherapy, taxane (docetaxel or Abraxane�) every 3 weeks, or Xeloda. Patients are then randomised to receive Avastin (15mg/kg every 2 weeks) or placebo (2:1 Avastin:placebo). Upon disease progression, patients may either continue on or cross over to Avastin plus chemotherapy at the investigator�s discretion. Further development of Bevacizumab in breast cancer is planned following the positive results of the US E2100 study. This phase III trial, to be conducted in countries worldwide, will investigate further combinations of Avastin and chemotherapy. The primary trial endpoint is progression-free survival. Investigators assign patients to a chemotherapy regimen, including specified regimens of anthracycline-based combination chemotherapy, taxane (docetaxel or Abraxane�) every 3 weeks, or Xeloda. Patients are then randomised to receive Avastin (15mg/kg every 2 weeks) or placebo (2:1 Avastin:placebo). Upon disease progression, patients may either continue on or cross over to Avastin plus chemotherapy at the investigator�s discretion.