Ninety seven (97) patients in the IFN alfa-2a arm and 131 patients in the Avastin arm reduced the dose of IFN alfa-2a from 9 MIU to either 6 or 3 MIU three times a week as pre-specified in the protocol. Dose-reduction of IFN alfa-2a did not appear to affect the efficacy of the combination of Avastin and IFN alfa-2a based on PFS event free rates over time, as shown by a sub-group analysis. The 131 patients in the Avastin + IFN alfa-2a arm who reduced and maintained the IFN alfa-2a dose at 6 or 3 MIU during the trial, exhibited at 6, 12 and 18 months PFS event free rates of 73, 52 and 21% respectively, as compared to 61, 43 and 17% in the total population of patients receiving Avastin + IFN alfa-2a.

AVF2938

This was a randomised, double-blind, phase II clinical trial investigating Avastin 10 mg/kg in a 2 weekly schedule with the same dose of Avastin in combination with 150 mg daily erlotinib, in patients with metastatic clear cell RCC. A total of 104 patients were randomised to treatment in this trial, 53 to Avastin 10 mg/kg every 2 weeks plus placebo and 51 to Avastin 10 mg/kg every 2 weeks plus erlotinib 150 mg daily. The analysis of the primary endpoint showed no difference between the Avastin + Placebo arm and the Avastin + Erlotinib arm (median PFS 8.5 versus 9.9 months). Seven patients in each arm had an objective response. The addition of erlotinib to bevacizumab did not result in an improvement in OS (HR = 1.764; p=0.1789), duration of objective response (6.7 vs 9.1 months) or time to symptom progression (HR = 1.172; p=0.5076).

AVF0890

This was a randomised phase II trial conducted to compare the efficacy and safety of bevacizumab versus placebo. A total of 116 patients were randomised to receive bevacizumab 3 mg/kg every 2 weeks (n=39), 10 mg/kg every 2 weeks; (n=37), or placebo (n=40). An interim analysis showed there was a significant prolongation of the time to progression of disease in the 10 mg/kg group as compared with the placebo group (hazard ratio, 2.55; p < 0.001). There was a small difference, of borderline significance, between the time to progression of disease in the 3 mg/kg group and that in the placebo group (hazard ratio, 1.26; p=0.053). Four patients had objective (partial) response, and all of these had received the 10 mg/kg dose bevacizumab; the ORR for the 10 mg/kg dose was 10%.

Epithelial ovarian, fallopian tube and primary peritoneal cancer

Front-line treatment of ovarian cancer

The safety and efficacy of Avastin in the front-line treatment of patients with epithelial ovarian, fallopian tube or primary peritoneal cancer were studied in two phase III trials (GOG-0218 and BO17707) that eva luated the effect of the addition of Avastin to carboplatin and paclitaxel compared to the chemotherapy regimen alone.

GOG-0218

The GOG-0218 study was a phase III multicentre, randomised, double-blind, placebo-controlled, three arm study eva luating the effect of adding Avastin to an approved chemotherapy regimen (carboplatin and paclitaxel) in patients with advanced (FIGO stages IIIB, IIIC and IV) epithelial o