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AVADO PFS Analysis (ITT Population) All P values vs. placebo Adapted from Miles et al. ASCO 2008, abstract LBA 1011.

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Presentation on theme: "AVADO PFS Analysis (ITT Population) All P values vs. placebo Adapted from Miles et al. ASCO 2008, abstract LBA 1011."— Presentation transcript:

1 AVADO PFS Analysis (ITT Population) All P values vs. placebo Adapted from Miles et al. ASCO 2008, abstract LBA 1011.

2 AVADO: Response (patients with measurable disease), % † mg/kg q3w Adapted from Miles et al. ASCO 2008, abstract LBA 1011.

3 E2100 and AVADO Serious Adverse Events (%) *ATE: arterial thromboembolic events. No increase in venous thromboembolic events was observed with bevacizumab in either study 1. Adapted from Miller et al. N Engl J Med 2007;357-2666-76. 2. Adapted from Miles et al. ASCO 2008, abstract LBA 1011.

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 Previously untreated MBC (n=722) Paclitaxel 90 mg/m 2 qw for 3 weeks of a 4-week cycle (n=354) Paclitaxel + bevacizumab 10 mg/kg q2w (n=368) Progressive disease (PD)* PD *No crossover permitted Adapted from Miller et al. N Engl J Med 2007;357:2666-76.

5 0.0 0.2 0.4 0.6 0.8 1.0 Months PFS proportion 0612182430 E2100 Trial: PFS Results HR=0.51 (0.43-0.62) Log rank test P<0.0001 Paclitaxel/bevacizumab: 11.4 months Paclitaxel: 6.11 months 484 events reported (89% of required events) 6.1111.4 Adapted from Miller et al. N Engl J Med 2007;357:2666-76.

6 E2100 Trial: Overall Response Rate Overall response rate (%) 339341262236 P<0.0001 Paclitaxel Paclitaxel/bevacizumab 13.8 29.9 16.0 37.7 0 10 20 30 40 All patientsMeasurable disease Adapted from Miller et al. N Engl J Med 2007;357:2666-76.

7 AVADO Study Design: Randomized, double-blind, placebo-controlled, multicentre, phase III trial Primary end point: PFS Secondary end points: overall response rate, duration of response, time to treatment failure, overall survival, safety and quality of life Previously untreated MBC (n=705) Docetaxel 100 mg/m 2 q3w + placebo PD Docetaxel + bevacizumab 7.5 mg/kg q3w Docetaxel + bevacizumab 15 mg/kg q3w Docetaxel was administered for a maximum of nine cycles but earlier discontinuation was permitted PD Adapted from Miles et al. ASCO 2008, abstract LBA1011. All patients were given the option to receive bevacizumab with second line chemotherapy

8 Adapted from Miles et al. ASCO 2008, abstract LBA1011. AVADO: Response (patients with measurable disease), % Placebo + docetaxel (n=207) Bev 7.5 † + docetaxel (n=201) Bev 15 † + docetaxel (n=206) Overall response rate P value (vs. control) 44 - 55 0.0295 63 0.0001 Best response CR 13 1 PR 4452 62 SD 3935 25 PD 125 4 † mg/kg q3w

9 Adapted from Miles et al. ASCO 2008, abstract LBA1011. AVADO: Safety Summary % Placebo + docetaxel (n=233) Bev 7.5 † + docetaxel (n=250) Bev 15 † + docetaxel (n=247) Any adverse events (AE)99.6100.099.6 Any grade ≥3 AE67.074.874.1 AEs leading to death* 2.61.6 AEs leading to discontinuation ‡ of Docetaxel 24.020.8 24.3 Bevacizumab or placebo 11.28.0 11.7 † mg/kg q3w; † during study phase; ‡ not mutually exclusive.

10 Adapted from Miles et al. ASCO 2008, abstract LBA1011. AVADO: Grade ≥3 Adverse Events of Special Interest,* % Adverse event, % Placebo+ docetaxel (n=233) Bev 7.5 † + docetaxel (n=250) Bev 15 † + docetaxel (n=247) All31.335.236.4 Neutropenia17.219.219.8 Febrile neutropenia 12.015.2 16.6 Venous thromboembolism 3.41.2 Hypertension 1.30.4 3.2 Bleeding 0.91.2 Wound-healing complication 0.90.4 GI perforation 0.90.4 Congestive heart failure 00.8 0 ATE 0.40 0 Proteinuria 00 0.4 RPLS** 00 0 * Protocol-defined; † mg/kg q3w; **RPLS=reversible posterior leuko encephalopathy syndrome

11 Ongoing RIBBON 1 Phase IIITrial Study Design Primary end point: hierarchical PFS Anthracycline-based combination chemotherapy, Q3w taxane (docetaxel or protein-bound paclitaxel) or capecitabine as determined by investigator prior to randomization † Chemotherapy regimen at investigator discretion Chemotherapy* + bevacizumab i.v. 15mg/kg q3w Chemotherapy* + placebo (i.v. on day 1 of 21-day cycle) Previously untreated MBC (n=950), 2:1 Randomization PD Chemotherapy † + bevacizumab i.v. 15mg/kg q3w or 10 mg/kg q2w Adapted from Albain K. ASCO 2008. Chemotherapy † + crossover to bevacizumab 15mg/kg q3w or 10 mg/kg q2w


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