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
Survival of Patients with Metastatic Breast Cancer 1974 - 2000
Months
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1990-1994
1985-1989
1980-1984
1974-1979
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1950s 1960s 1970s 1980s 1990sN
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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