Bevacizumab in MBC 1 Breast Cancer Take home message Sabino De Placido.

Bevacizumab in MBC

1

Breast Cancer

Take home message

Sabino De Placido

Survival of Patients with Metastatic Breast Cancer 1974 - 2000

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International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent ChemotherapyFatima Cardoso , Philippe L. Bedard , Eric P. Winer , Olivia Pagani , Elzbieta Senkus-Konefka , Lesley J. Fallowfield , Stella Kyriakides , Alberto Costa , Tanja Cufer , Kathy S. Albain ; on behalf of the ESO-MBC Task Force

J Natl Cancer Inst 2009;101:1174–1181

In the absence of evidence to guide daily clinical decision making in MBC, both combination and sequential single agent chemotherapy are reasonable options as first-line systemic therapy.

An important question for future research is the clear definition of patients who may benefit from a combination approach. Until such data are available, the ESO-MBC Task Force believes that sequential single-agent therapy should be the preferred choice for most MBC patients, in the absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control. These recommendations reflect consensus expert opinion and represent level 5 clinical evidence.

4

Metastatic Breast Cancer

Take home message

No single «gold standard» in metastatic breast cancer

1/5

Bevacizumab in first line MBC

5

Breast Cancer

BV=bevacizumab, PL=placebo, PFS=progression-free survival, ORR=objective response rate, OS=overall survival.* Permitted continuing on BV or crossing over to BV.† Analyses based on IRF assessments.

Comparison of the Studies (1/2)

E2100 AVADO* RIBBON-1*

No. of patients 722 488 1237

Geography US (90%) Ex-US US (50%)

Randomization ratio (BV:PL)

1:1 1:1 2:1

Primary Endpoint PFS† PFS PFS

Independent review Retrospective No Prospective

Comparison of the Studies (2/2)

E21001 AVADO2 RIBBON-13

Placebo controlled

No Yes Yes

Chemotherapy Weekly paclitaxel

3-weekly docetaxel

CapecitabineTaxane or

anthracycline

Bevacizumab dose

10 mg/kg q2w 7.5 or 15 mg/kg q3w 15 mg/kg q3w

Key Secondary Endpoints

OS, ORROS, ORR,

1-yr survivalOS, ORR,

1-yr survival

1. Miller, et al. NEJM 2007; 2. Miles, et al. ASCO 2008; 3. Robert, et al. ASCO 2009

8

Metastatic Breast Cancer

Take home message

Remarkable consistency in all study results

Study Results

2/5

Consistent Benefit with Bevacizumab-Based Therapy: Significant Improvement in PFS

E2100 AVADORIBBON-1

(Cape)RIBBON-1

(Tax/Anthra)

Non-BV

BVNon-BV

BV*Non-BV BV

Non-BV BV

Median PFS, mo

5.8 11.3 7.9 8.8 5.7 8.6 8.0 9.2

StratifiedHR (95% CI)

0.48(0.39–0.61)

0.62(0.48–0.79)

0.69(0.56–0.84)

0.64(0.52–0.80)

p-values p<0.0001 p=0.0003 p=0.0002 p<0.0001

BV=bevacizumab, Cape=capecitabine, Tax/Anthra=taxane/anthracycline.* 15 mg/kg cohort.

E2100 AVADORIBBON-1

(Cape)RIBBON-1

(Tax/Anthra)

Non-BV

BVNon-BV

BV*Non-BV BV

Non-BV BV

ORR (%) 23 41 46 64 23.6 35.4 37.9 51.3

p-values p<0.0001 p=0.0003 p=0.0097 p<0.0054

BV=bevacizumab, Cape=capecitabine, Tax/Anthra=taxane/anthracycline.* 15 mg/kg cohort.

Consistent Benefit with Bevacizumab-Based Therapy: Significant Improvement in ORR

E2100 AVADO RIBBON-1 (Cape)

RIBBON-1(Tax/Anthra)

Non-BV

BVNon-BV

BV* Non-BV BV Non-BV BV

Median OS, mo

24.8 26.5 31.9 30.2 21.2 29.0 23.8 25.2

StratifiedHR (95% CI)

0.87 1.03 0.85 1.03

p-values P=0.14 P=0.85 P=0.87 P=0.83

1 year rate (%)

74 81 76 84 74 81 83 81

p-values P=0.017 P=0.02 P=0.076 P=0.44

BV=bevacizumab, Cape=capecitabine, Tax/Anthra=taxane/anthracycline.* 15 mg/kg cohort.

No Statistically Significant Difference in OS

A Meta-Analysis of Overall Survival Data from Three Trials of Bevacizumab and First-Line

Chemotherapy as Treatment for Patients with Metastatic Breast Cancer

Baylor-Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX; Mount Vernon Cancer Centre, London, England; Dana-Farber Cancer Institute, Boston, MA; Institut Curie, Paris, France; Mayo Clinic, Jacksonville, Florida; Michiana Hematology Oncology, South Bend, IN; Vall d'Hebron

University Hospital, Barcelona, Spain; BioOncology, Genentech, S San Francisco, CA; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN

Joyce O’Shaughnessy, David Miles, Robert Gray, Véronique Diéras, Edith A. Perez, Robin Zon, Javier Cortés,

Xian Zhou, See-Chun Phan, Kathy Miller

ASCO, 2010

General Study Designs

OptionalSecond-line

Chemo + BV

(AVADO and RIBBON-1

only)

Chemo +No BV

Chemo +BV

Treat untilPD

RA

ND

OM

IZE

Previously Untreated

MBC

RIBBON-1Capecitabine,

Taxane,or

Anthracycline

AVADODocetaxel

E2100Paclitaxel

Progression-Free Survival, Pooled Population

Non-BV(n=1008)

BV(n=1439)

Median, mo 6.7 9.2

HR (95% CI) 0.64 (0.57–0.71)

• PFS

- HR=0.64, 36% reduction in risk of PD or death

- 2.5 month improvement in median PFS

- Improvements across key clinical subpopulations

• ORR

- 17% increase vs controls

• OS

- No statistically significant difference

Summary of Pooled Efficacy Analysis

16

Metastatic Breast CancerClinical Relevance

Clinical Relevance

18

Metastatic Breast Cancer

Take home message

The improvement in PFS is similar to that of most other first line studies

Clinical Relevance

3/5

19

Metastatic Breast CancerAdverse Events

20

E2100, AVADO & RIBBON1 MetanalysisGrade ≥3 Selected Adverse Events (Aes)

21

Metastatic Breast Cancer

Take home message

Well tolerated in MBC patients and AE are fairly manageable

Adverse Events

4/5

22

Metastatic Breast CancerImprovements across key clinical subpopulations

27

Metastatic Breast CancerImprovements across key clinical subpopulations

Take home message

5/5

The advantage may be relevant in triple negative breast cancer