28th Annual San Antonio Breast Cancer SymposiumDecember 8-11, 2005; San Antonio, Texas

Summarized byKathy Miller, MD

Indiana University School of MedicineIndianapolis, Indiana

Angiogenic Therapy for Breast Cancer

Supported by an unrestricted educational grant from

Stratify:• DFI < 24 months vs > 24 months• < 3 vs > 3 metastatic sites• Adjuvant chemotherapy, yes vs no• ER+ vs ER- vs ER-unknown

RANDOMIZE

Paclitaxel + Bevacizumab

Paclitaxel

E2100: A Randomized Phase 3 Trial of Paclitaxel vs Paclitaxel + Bevacizumab for Advanced Breast Cancer

28-day cycle:

Paclitaxel 90 mg/m2 D1, 8, and 15

Bevacizumab 10 mg/kg D1 and 15

Miller et al. Breast Cancer Res Treat. 2005;95(suppl 1):S6. Abstract 3.

E2100: Patient Characteristics

Paclitaxel

(n=339)

Pac + Bev

(n=341)

Median age 55 (27-85) 56 (29-84)

DFI < 24 months 42% 42%

> 3 sites 43% 43%

Adjuvant chemotherapy

Taxane

64%

18%

65%

18%

ER+

HER2+

64%

4%

59%

5%

Miller et al. Breast Cancer Res Treat. 2005;95(suppl 1):S6. Abstract 3.

All patients Measurable Disease0

10

20

30

40

PaclitaxelPac + Bev

Ove

rall

Res

po

nse

Rat

eE2100: Response

339 236341 262

37.7%

16%

29.9%

13.8%

P < .0001P < .0001

Miller et al. Breast Cancer Res Treat. 2005;95(suppl 1):S6. Abstract 3.

0.0

0.2

0.4

0.6

0.8

1.0

Months

PF

S P

rob

ab

ility

0 6 12 18 24 30

E2100: Progression-Free Survival

HR = 0.51 (0.43-0.62)

Log Rank Test P <0 .0001

Pac + Bev 11.4 months

Paclitaxel 6.11 months

484 events reported

Miller et al. Breast Cancer Res Treat. 2005;95(suppl 1):S6. Abstract 3.

E2100: Bevacizumab ToxicityNCI-CTC Grade 3 and 4

Paclitaxel(n=332)

Pac + Bev(n=350)

%

Grade 3 Grade 4 Grade 3 Grade 4

Hypertension* 2 0 15 < 1

Thromboembolic 2 2 2 0

Bleeding* 0 0 2 < 1

Proteinuria* 0 0 1 1

Neuropathy 17 1 22 1

Fatigue* 4 < 1 8 < 1

Miller et al. Breast Cancer Res Treat. 2005;95(suppl 1):S6. Abstract 3.

*Toxicities significantly increased with bevacizumab

E2104 Adjuvant Pilot Trial

REGISTER

Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 Bevacizumab 10 mg/kgevery 14 days x 4

Arm A: dose-dense BAC > BT > B

Arm B: dose-dense AC >BT>B

Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 every 14 days x 4

Paclitaxel 175 mg/m2 Bevacizumab 10 mg/kg every 14 days x 4

Paclitaxel 175 mg/m2 Bevacizumab 10 mg/kg every 14 days x 4

Bevacizumab 10 mg/kg every 14 days x 18

Bevacizumab 10 mg/kg every 14 days x 22

*Hormone therapy and radiation per standard care

Randomized Phase 2 Trial of Metronomic Chemotherapy +/- Bevacizumab

R

CM aloneCyclophosphamide 50 mg orally, daily Methotrexate 2.5 mg orally, twice a day, days 1, 2 each week

CM + bevacizumabCyclophosphamide 50 mg orally, dailyMethotrexate 2.5 mg orally, twice a day, days 1, 2 each weekBevacizumab 10 mg/kg intravenously every 14 days

Option of crossoverupon progression

Burstein et al. Breast Cancer Res Treat. 2005;94(suppl 1):S6. Abstract 4.

< 1 prior chemo for MBC

Phase 2 Metronomic CM vs CM + Bevacizumab: Patient Characteristics

CM alone

N=21

CM + Bevacizumab

N=34

Median age 50.3 (34-59) 51.5 (34-76)

ER+ 14 67% 21 62%

HER2+ 2 10% 0 0%

Visceral Dx 10 48% 24 71%

Adj Chemo 15 72% 30 88%

1 chemo for MBC

10 48% 16 47%

Prior A 16 76% 28 82%

Prior T 11 52% 18 53%

Burstein et al. Breast Cancer Res Treat. 2005;94(suppl 1):S6. Abstract 4.

Phase 2 Metronomic CM vs CM + Bevacizumab: Best Overall Response

CM alone

N=21

CM + Bevacizumab

N=34

N % 95% CI N % 95% CI

PR 2 10% 1% to 30%

10 29% 15% to 50%

SD 8 38% 14 41%

PD 9 43% 9 26%

N/A 2 10% 1 3%

TTP 2.0 months 5.5 months

Burstein et al. Breast Cancer Res Treat. 2005;94(suppl 1):S6. Abstract 4.