Bevacizumab in MBC 1 Breast Cancer Take home message Sabino De Placido.
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Transcript of Bevacizumab in MBC 1 Breast Cancer Take home message Sabino De Placido.
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Bevacizumab in MBC
1
Breast Cancer
Take home message
Sabino De Placido
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Survival of Patients with Metastatic Breast Cancer 1974 - 2000
Months
60483624120
Cum
ulat
ive
Surv
ival
1.0
.8
.6
.4
.2
0.0
1995-2000
1990-1994
1985-1989
1980-1984
1974-1979
0
5
10
15
20
25
30
1950s 1960s 1970s 1980s 1990sN
o. D
rug
s A
va
ilab
le
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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.
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4
Metastatic Breast Cancer
Take home message
No single «gold standard» in metastatic breast cancer
1/5
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Bevacizumab in first line MBC
5
Breast Cancer
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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
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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
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8
Metastatic Breast Cancer
Take home message
Remarkable consistency in all study results
Study Results
2/5
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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.
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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
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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
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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
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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
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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)
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• 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
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16
Metastatic Breast CancerClinical Relevance
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Clinical Relevance
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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
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19
Metastatic Breast CancerAdverse Events
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20
E2100, AVADO & RIBBON1 MetanalysisGrade ≥3 Selected Adverse Events (Aes)
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21
Metastatic Breast Cancer
Take home message
Well tolerated in MBC patients and AE are fairly manageable
Adverse Events
4/5
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22
Metastatic Breast CancerImprovements across key clinical subpopulations
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27
Metastatic Breast CancerImprovements across key clinical subpopulations
Take home message
5/5
The advantage may be relevant in triple negative breast cancer
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