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December 6-10, 2011
San Antonio, Texas
An Update on Early Breast
CancerCCO Independent Conference Coverageof the 2011 Annual Meeting of the AACR-CTRC San Antonio
Breast Cancer Symposium*
This program is supported by educational grants from
*CCO is an independent medical education company that
provides state-of-the-art medical information to healthcare
professionals through conference coverage and other
educational programs.
Jointly sponsored/Co-provided by the Annenberg Center for Health
Sciences at Eisenhower and Clinical Care Options, LLC
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About These Slides
In the following slides, you will find highlights of the keystudies from this meeting. Be sure to review the slidenotes field for each slide for insightful commentaryfrom our expert faculty
Users are encouraged to use these slides in their own noncommercialpresentations, but we ask that content and attribution not be changed. Users areasked to honor this intent
These slides may not be published or posted online without permission fromClinical Care Options (email [email protected])
Disclaimer
The materials published on the Clinical Care Options Web site reflect the views of the authors of the
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educational grants. The materials may discuss uses and dosages for therapeutic products that have not
been approved by the United States Food and Drug Administration. A qualified healthcare professional
should be consulted before using any therapeutic product discussed. Readers should verify all information
and data before treating patients or using any therapies described in these materials.
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An Update on Early Breast Cancer
Faculty
Joyce OShaughnessy, MDCo-Director, Breast Cancer ResearchBaylor Charles A. Sammons Cancer CenterTexas Oncology
US OncologyDallas, Texas
Peter Ravdin, MD, PhDDirector of the Breast Cancer Program
The University of Texas Health Science Center at San AntonioSan Antonio, Texas
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Disclosures
Joyce OShaughnessy, MD, has disclosed that she hasreceived consulting fees from Biogen Idec, BoehringerIngelheim, Bristol-Myers Squibb, Caris Diagnostics, Eisai,Genentech, GlaxoSmithKline, GTx, Johnson & Johnson,Roche, and sanofi-aventis and fees for non-CME servicesfrom Bristol-Myers Squibb, Celgene, and sanofi-aventis.
Peter Ravdin, MD, PhD, has disclosed that he has anownership interest in Adjuvant, Inc.
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An Update on Early Breast Cancer
Overview of Early Breast Cancer
Adjuvant Therapy
TEACH: lapatinib vs placebo
Bisphosphonate trials
7-yr update of ABCSG-12
5-yr update of ZO-FAST
NSABP B-34: clodronate vs placebo
GAIN: ibandronate vs placebo
Neoadjuvant Therapy
GeparTrio Trial : response-guided vs conventional chemotherapy
Prognosis and Prediction
DCIS score and risk of recurrence
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Adjuvant Therapy
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Women with resected
HER2-positive
stage I-IIIc primarybreast cancer and no
previous trastuzumab
therapy
(N = 3147)
Lapatinib 1500 mg once daily
(n = 1571)
Placebo
(n = 1576)
Yr 1
Stratified by time from diagnosis,
lymph node involvement,hormone receptor status
Goss P, et al. SABCS 2011. Abstract S4-7.
TEACH: Study Design
Primary endpoint: DFS
Secondary endpoints: OS, recurrence-free survival, distant recurrence-freesurvival
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TEACH: Risk of Recurrence in Patients
Without Anti-HER2 Therapy
Goss P, et al. SABCS 2011. Abstract S4-7.
Yr(s) Disease-FreePatients, %
1 99.9
2 96.7
3 93.14 91.0
5 87.8
6 84.4
7 81.1
8 79.2
9 77.2
10 74.9
0
1.0
0.9
0.8
0.7
0.60.5
0.4
0.3
0.2
0.1ProportionofPatients
WithDF
S
Yrs
0 1 2 3 4 5 6 7 8 9 10
Placebo
Patients at Risk, n
1576 1569 1504 1430 1323 1043 781 539 310 181 96
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TEACH: DFS and OS
No improvement in OS demonstrated with use of lapatinib:HR: 0.99 (95% CI: 0.74-1.31; P= .966)
DFS With Lapatinib vs Placebo Patients, n HR (95% CI) PValue
Overall population 3147 0.83 (0.70-1.00) .053
Time since diagnosis
< 1 yr 647 0.70 (0.50-0.99)
4 yrs 2248 0.84 (0.69-1.03)
> 4 yrs 899 0.81 (0.52-1.26)
Hormone receptor status, %
ER and/or PgR positive 1859 0.98 (0.77-1.25) .886
ER and PgR negative 1288 0.68 (0.52-0.89) .006
Lymph node involvement Positive 1753 0.86 (0.69-1.07)
Negative 1394 0.78 (0.57-1.07)
Goss P, et al. SABCS 2011. Abstract S4-7.
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An Update on Early Breast Cancer
TEACH: DFS in Patients With Centrally
Confirmed HER2+ Disease
Goss P, et al. SABCS 2011. Abstract S4-7.
Outcome Lapatinib,%
(n = 1230)
Placebo,%
(n = 1260)
DFS HR(95% CI)
PValue
All DFS events 13 17 0.82(0.67-1.00)
.04
Local 2 3
Regional 2 2
Distant 8 11
CNS recurrence < 1 2 0.66(0.33-1.34)
.286
Contralateral breast < 1 1
Second primarymalignancy
2 2
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TEACH: Safety
Lapatinib associated with more treatment discontinuation (20%vs 6%), adjustment/interruption (29% vs 9%) vs placebo
No difference in incidence of cardiac events between lapatinib
and placebo arms (3% vs 3%)
Goss P, et al. SABCS 2011. Abstract S4-7.
Adverse Events, % Lapatinib
(n = 1573)
Placebo
(n = 1574)
Grade 1/2 Grade 3/4 Grade 1/2 Grade 3/4
Diarrhea 55 6 16 1Rash 54 6 15 1
Nausea 17 1 11 1
Fatigue 15 1 13 1
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TEACH: Conclusions
Adjuvant lapatinib after resection of early HER2+ breast cancer failedto show significant statistical improvement in DFS, OS vs placebo
Patients with no previous treatment with trastuzumab
DFS benefit with lapatinib observed in 2 patient subgroups
Patients with hormone receptornegative disease
Patients receiving lapatinib within 1 yr of primary diagnosis
HER2 status reassessed by central review
HER2-positive confirmed by FISH: 79%
Significant improvement in DFS with lapatinib in this subset of patients
Most common AEs associated with lapatinib: diarrhea and rash
Goss P, et al. SABCS 2011. Abstract S4-7.
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ABCSG-12: Study Design
Key endpoints
Primary: DFS at 5 yrs
Secondary: relapse-free survival, OS, bone mineral density, safety
TAM 20 mg/day
ANA 1 mg/day
1803 premenopausal patientswith breast cancer, stage I/II(goserelin 3.6 mg/ 28 days)
Stratified by: ER+ and/or PgR+ Age Stage Grade Lymph nodes Treatment 3 yrs
(median follow-up: 48 mos)
TAM + ZOL 4 mg q6m
ANA + ZOL 4 mg q6m
R
Long-term
monitoring
for 5 yrs for
recurrence
and survival(DFS, OS)
3-yr
BMD
5-yr
BMDGnant M, et al. N Engl J Med. 2009;360:679-691.
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DFS
ABCSG-12 (84 Mos): Efficacy
100
80
60
40
20
0
DFS(%)
0 12 24 36 48 60 72 84 96 108
Mos Since Randomization
Pts at Risk, n
No ZOL
ZOL
903
900
858
862
833
841
807
822
758
788
653
674
521
544
405
419
191
208
Events,
n
Univariate Multiple CoxRegression
HR
(95% CI)
P
Value
HR
(95% CI)
P
Value
vs no
ZOL
vs no
ZOL
(Log-
rank)No
ZOL
132/903
0.72
(0.56-0.94)
.014 0.71
(0.55-0.92)
.01198/900ZOL
OS
100
80
60
40
20
0
OS(%)
0 12 24 36 48 60 72 84 96 108
Mos Since Randomization
Pts at Risk, n
No ZOL
ZOL
903
900
864
868
856
858
839
849
811
818
706
708
576
587
456
454
215
232
Events,
n
Univariate Multiple CoxRegression
HR
(95% CI)
P
Value
HR
(95% CI)
P
Value
vs no
ZOL
vs no
ZOL
(Mantel
-Cox)No
ZOL
49/903
0.63
(0.40-0.99)
.049 0.61
(0.39-0.96)
.03333/900ZOL
Gnant M, et al. SABCS 2011. Abstract S1-2
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Gnant M, et al. SABCS 2011. Abstract S1-2
ABCSG-12 (84 Mos): First DFS Events
140
120
100
80
60
40
20
0
F
irstEvent/Patient
(n)
No ZOL
(n = 903)
ZOL
(n = 900)
Death without
previous recurrence
Secondary
malignancy
Contralateralbreast cancer
Distant
recurrence
Locoregional
recurrence
19
56
11
14
36
65
13
18
3
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Gnant M, et al. SABCS 2011. Abstract S1-2.
ABCSG-12 (84 Mos): Age Effect on DFS
40 Yrs of Age or Younger Older Than 40 Yrs of Age
100
80
60
40
20
0
DFS(%)
0 12 24 36 48 60 72 84 96 108
Mos Since Randomization
Pts at Risk, n
No ZOL
ZOL
213
200
202
192
194
185
189
180
177
169
157
148
127
125
102
94
52
48
Events, n
Univariate
HR (95% CI) PValue
vs no ZOL (Log-rank)No ZOL 42/213
0.87 (0.55-1.36) .52535/200ZOL
100
80
60
40
20
00 12 24 36 48 60 72 84 96 108
Mos Since Randomization
Pts at Risk, n
No ZOL
ZOL
690
700
656
670
639
656
616
642
581
619
496
526
394
419
303
325
139
160
Events, n
Univariate
HR (95% CI) PValue
vs no ZOL (Log-rank)No ZOL 90/690
0.66 (0.48-0.92) .01363/700ZOL
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ABCSG-12: Conclusions
Survival benefits with addition of ZOL to endocrine therapyfirst reported at median follow-up of 48 mos are still presentat 84 months
Significant improvement in DFS
Relative risk reduction: 28%
Significant improvement in OS
Relative risk reduction: 37% Subanalysis suggests that survival benefits of ZOL may be
restricted to patients older than 40 yrs of age
Gnant M, et al. SABCS 2011. Abstract S1-2.
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An Update on Early Breast Cancer
Letrozole +
Zoledronic Acid 4 mg
q6m
Letrozole + Delayed*
Zoledronic Acid 4 mg
q6m
*If 1 of the following occurs:BMD T score < -2 SDClinical fractureAsymptomatic fracture at 36 mos
Stage I-IIIa breast cancer
Postmenopausal oramenorrheic due to
cancer treatment ER+ and/or PgR+ T-score -2 SD N = 1065
Treatment duration 5 yrs
De Boer R, et al. SABCS 2011. Abstract S1-3.
ZO-FAST: 5-Yr Final Analysis
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De Boer R, et al. SABCS 2011. Abstract S1-3.
ZO-FAST (Primary Endpoint): Median
Change in Lumbar Spine BMDImmediate ZOL
Delayed ZOLP< .0001 for each
Change
inLS(LS-L4)BMD(%)
12 mos 24 mos 36 mos 48 mos 60 mos-6
-4
-2
0
2
4
6
360
369
339 313290
264
343 311 294 264
5.9% 8.2% 8.8% 9.2% 10.0%
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*Censored patients at initiation of delayed ZOL (n = 144).
Time on Study (Mos)
532
533
518
511
500
491
488
475
475
463
376
368IM-ZOL
D-ZOL
Pts at Risk, n Time on Study (Mos)
532
533
518
459
500
402
488
376
475
350
376
267
IM-ZOL
D-ZOL
Pts at Risk, n
ITT Population
100
90
80
70
6050
40
30
20
10
0
DFS(%
)
0 6 12 18 24 30 36 42 48 54 60 66
HR: 0.66; log-rank P= .0375
IM-ZOL 4 mg (42 events)D-ZOL 4 mg (62 events)
Censored Analysis*
100
90
80
70
6050
40
30
20
10
0
DFS(%
)
0 6 12 18 24 30 36 42 48 54 60 66
HR: 0.62; log-rank P= .024
IM-ZOL 4 mg (42 events)D-ZOL 4 mg (53 events)
De Boer R, et al. SABCS 2011. Abstract S1-3.
ZO-FAST: Final 5-Yr DFS
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ZO-FAST: Disease Recurrence
De Boer R, et al. SABCS 2011. Abstract S1-3.
DistantContralateral
Key Sites of DistantRecurrence*
Patients(n)
D-ZOL(n = 533)
0
10
40
50
70
12
Local
LiverLung
Lymph nodeBone
Disease Recurrence
IM-ZOL(n = 532)
53
29
6
41
20
30
60
Patients(n)
D-ZOL(n = 533)
0
10
40
50
70
24
IM-ZOL(n = 532)
145
9
11
9
20
30
60
119
*Multiple sites may be recorded within the same patient.
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OS(%)
100
90
80
70
60
50
40
30
20
10
00 6 12 18 24 30 36 42 48 54 60 66
HR: 0.69; log-rank P= .196
Time on Study (Mos)
532
533
522
519
511
505
502
491
485
480
406
407
IM-ZOL
D-ZOL
Pts at Risk, n
IM-ZOL 4 mg (26 events)D-ZOL 4 mg (36 events)
De Boer R, et al. SABCS 2011. Abstract S1-3.
ZO-FAST: Overall Survival (ITT
Population)
A U d E l B C
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ZO-FAST: Conclusions
Immediate initiation of ZOL at start of letrozole significantlyprolonged DFS vs delayed initiation of ZOL inpostmenopausal women with endocrine-responsive EBC[1]
Continued to improve BMD after 5 yrs of follow-up
34% improvement in DFS
Findings consistent with those observed in ABCSG-12 andsubset of patients > 5 yrs postmenopause in AZURE[2,3]
1. De Boer R, et al. SABCS 2011. Abstract S1-3. 2. Coleman RE, et al. N Engl J Med. 2011;365:1396-1405. 3.
Gnant M, et al. SABCS 2011. Abstract S1-2.
A U d t E l B t C
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HR
ZO-FAST[1]
104 events
ABCSG-12[3]
230 events
0.2 0.4 0.6 0.8 1.0 1.2 1.4
N = 1803
N = 1065
n = 1041AZURE: > 5 yrs postmenopausal[2]
263 events
PValue
.02
.0375
.011
0.75
0.66
0.71
Zoledronic Acid Studies: DFS Comparison
1. De Boer R, et al. SABCS 2011. Abstract S1-3. 2. Coleman RE, et al. N Engl J Med. 2011;365:1396-1405. 3.
Gnant M, et al. SABCS 2011. Abstract S1-2.
A U d t E l B t C
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Women with stage I-III
breast cancer
(N = 3323)
Clodronate 1600 mg/day*
(n = 1662)
Placebo*
(n = 1661)
3 YrsStratified by age, number of positive
nodes, and ER/PgR status
*All patients could receive adjuvant systemic chemotherapy with or without tamoxifen or no adjuvant
therapy at investigator discretion.
Paterson A, et al. SABCS 2011. Abstract S2-3.
NSABP B-34: Phase III Study of Adjuvant
Clodronate in Breast Cancer Primary endpoint: DFS (mean follow-up: 8.4 yrs)
Two thirds aged 50 yrs or older; 25% node positive
A U d t E l B t C
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NSABP B-34: Analysis of Specified
EndpointsEndpoint Events, n HR (95% CI) PValue
Clodronate(n = 1655)
Placebo(n = 1656)
DFS 286 312 0.913 (0.778-1.072) .266
OS 140 167 0.842 (0.672-1.054) .131
RFI 148 177 0.834 (0.671-1.038) .101
BMFI 61 80 0.765 (0.548-1.068) .114
NBMFI 78 105 0.743 (0.554-0.996) .046
Paterson A, et al. SABCS 2011. Abstract S2-3.
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NSABP B-34 Subset Analysis: DMFI, RFI,
BMFI, NBMFI in Pts Aged > 50 YrsEndpoint for Patients Aged50 Yrs or Older
HR PValue
DMFI 0.62 .003
RFI 0.76 .05
BMFI 0.61 .024
NBMFI 0.63 .015
Paterson A, et al. SABCS 2011. Abstract S2-3.
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NSABP B-34: Conclusions
No significant benefit in DFS (primary endpoint) with oralclodronate in women with early breast cancer[1]
Clodronate significantly reduced NBMFI vs placebo[1]
HR: 0.743; 95% CI: 0.554-0.996; P= .046
In patients aged 50 yrs or older, clodronate associated withsignificant improvements in RFI, BMFI, NBMFI vs placebo[1]
Findings consistent with those observed in older, postmenopausal
women in other adjuvant bisphosphonate studies[2-4]
Adverse events similar in clodronate and placebo arms[1]
1. Paterson A, et al. SABCS 2011. Abstract S2-3. 2. De Boer R, et al. SABCS 2011. Abstract S1-3.
3. Coleman RE, et al. N Engl J Med. 2011;365:1396-1405. 4. Gnant M, et al. SABCS 2011. Abstract S1-2.
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Patients aged 65 yrs or
younger with previouslyuntreated node-positive
primary breast cancer
(N = 3023)
Ibandronate 50 mg/day PO
(n = 2015)
Observation
(n = 1008)
Yr 2Randomized 2:1*
*Patients in trial also randomized 1:1 to receive ETC vs epirubicin/cyclophosphamide followed by paclitaxel/capecitabine
(EC-TX).
ECT regimen: epirubicin 150 mg/m2 every 2 wks for 3 cycles, followed by paclitaxel 225 mg/m2 every 2 wks for 3 cycles,
followed by cyclophosphamide 2000 mg/m2 every 2 wks for 3 cycles.
EC-TX regimen: concurrent epirubicin 112.5 mg/m2 and cyclophosphamide 600 mg/m2 every 2 wks for 4 cycles, followed by
concurrent paclitaxel 67.5 mg/m2 wkly for 10 wks and capecitabine 2000 mg/m2 on Days 1-14 every 3 wks for 4 cycles.
During chemotherapy, all patients received primary prophylaxis with pegfilgrastim and either epoetin or darbepoetin.
Mobus V, et al. SABCS 2011. Abstract S2-4.
German GAIN Trial: Study Design
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GAIN: Patient Characteristics
Mobus V, et al. SABCS 2011. Abstract S2-4.
Characteristic Ibandronate(n = 1996)
Observation(n = 998)
Age, median yrs 49 50
Premenopausal, % 48.4 47.2
pT4, % 2.1 1.4
pN1, % 38.1 37.1
pN2, % 34.9 36.3
pN3, % 27.0 26.7
Mastectomy, % 44.5 43.3
Ductal invasive, % 77.4 77.1
Grade 3, % 47.3 44.3
Hormone receptor positive, % 76.5 77.7
HER2 positive, % 22.1 21.8
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GAIN: DFS and OS (ITT)
Mobus V, et al. SABCS 2011. Abstract S2-4.
1.0
0.8
0.6
0.4
0.2
0
SurvivalProbability
DFS (Mos)
0 12 24 36 48 60
1996
998
1814
871
1590
727
1057
483
555
264
210
105
3-yrDFS:
Ibandronate 87.6%
Observation: 87.2%
Cox regression:
HR: 0.945 (95% CI: 0.768-1.16; P= .59)
Ibandronate Observation
Product-Limit Survival Estimates
With Number of Subjects at Risk
+ Censored1.0
0.8
0.6
0.4
0.2
0
OS (Mos)
0 12 24 36 48 60
1996
998
1836
886
1653
756
1121
506
586
277
219
112
3-yrOS:
Ibandronate 94.7%
Observation: 94.1%
Cox regression:
HR: 1.04 (95% CI: 0.763-1.42; P= .80)
Product-Limit Survival Estimates
With Number of Subjects at Risk
+ Censored
Pts at risk, n Pts at risk, n
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GAIN: Subgroup Analyses
Mobus V, et al. SABCS 2011. Abstract S2-4.
DFS for Ibandronate in Subgroups
HR
0.5 1.0 1.5
Better with ibandronate Worse with ibandronate
pN1
pN2
pN3ER and/or PgR positive
ER and PgR negative
Pre- and perimenopausal
Postmenopausal
< 60 yrs
60 yrs
HR: 1.04 (95% CI: 0.652-1.65; P= .877)
HR: 0.875 (95% CI: 0.599-1.28; P= .490)
HR: 0.951 (95% CI: 0.710-1.27; P= .734)HR: 0.952 (95% CI: 0.736-1.23; P= .706)
HR: 0.856 (95% CI: 0.604-1.21; P= .383)
HR: 1.02 (95% CI: 0.756-1.37; P= .912)
HR: 0.897 (95% CI: 0.671-1.20; P= .462)
HR: 1.02 (95% CI: 0.807-1.30; P= .842)
HR: 0.746 (95% CI: 0.490-1.14; P= .172)
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GAIN: Conclusions
Adjuvant ibandronate did not improve DFS nor OS followingdose-dense chemotherapy in patients with node-positiveprimary breast cancer
GAIN trial still ongoing to compare the 2 different dose-dense chemotherapy regimens
Mobus V, et al. SABCS 2011. Abstract S2-4.
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Trial Regimen Primary Outcomes
SWOG 0307 ZOL vs clodronate vs ibandronate DFS, OS
NATAN ZOL after neoadjuvant chemo EFS
D-CARE Dmab 120 mg/mo for 6 mos, then 120mg q3m vs placebo
Bone metastasisfreesurvival
HOBOE Triptorelin + tamoxifen vstriptorelin + letrozole vs
triptorelin + letrozole + ZOL
DFS
SUCCESS FEC-D vs FEC-DG
2 yrs ZOL vs 5 yrs ZOL
DFS
ABCSG-18 Dmab 60 mg q6m vs placebo Time to first fracture
Ongoing Phase III Trials of Antitumor
Properties of Bone-Targeted Agents
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Neoadjuvant Therapy
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Women with
operable or locally
advanced
breast cancer
(N = 2072)
TAC-NX*
(4 cycles NX)
(n = 301)
TAC x 6
(4 additional cycles TAC)(n = 321)
TAC x 6
(4 additional cycles TAC)
(n = 704)
TAC x 8
(6 additional cycles TAC)
(n = 686)
TAC*
(2 cycles)
Assess
response
Minimal
response
(n = 622)
CR or PR
(n = 1390)
*TAC regimen: docetaxel 75 mg/m2, doxorubicin 50 mg/m2,
cyclophosphamide 500 mg/m2 all on Day 1 q21d.
NX regimen: vinorelbine 25 mg/m2 on Days 1 and 8,
capecitabine 1000 mg/m2 on Days 1-14 q21d.Response assessed by ultrasound/palpation.< 50% tumor reduction.
Von Minckwitz G, et al. SABCS 2011. Abstract S3-2.
GeparTrio Trial: Study Design
Not working?
Try another type
of chemotherapy
Working?
Give more of the same
chemotherapy
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GeparTrio Trial: DFS and OS
Median follow-up: 62 mos
DFS benefit in early responding and nonresponding patients whoreceived response-guided vs conventional chemotherapy
Von Minckwitz G, et al. SABCS 2011. Abstract S3-2.
Endpoint HR for Response-Guided vsConventional Chemotherapy (95% CI)
PValue
DFS 0.71 (0.60-0.85) < .001
OS 0.79 (0.63-0.99) .048
Patient Subgroup Treatment Comparison HR for DFS
(95% CI)
PValue
Responders TAC x 8 vs TAC x 6 0.78 (0.62-0.97) .026
Nonresponders TAC-NX vs TAC x 6 0.59 (0.49-0.82) .001
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GeparTrio Trial: DFS by Patient Subgroup
Response-guided treatments better Conventional treatments better
0.2 0.4 0.6 0.8 1.0 1.2 1.4
Subgroup
OverallAge (yrs)
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p y
GeparTrio Trial: pCR by Breast Cancer
Subtype
Von Minckwitz G, et al. SABCS 2011. Abstract S3-2.
pCR(%)
40
35
30
25
20
15
10
5
0
Luminal A (n= 572)
Luminal B(HER2-)(n = 211)
Luminal B(HER2+)(n = 281)
HER2+(Nonluminal)
(n = 178)
Triple Negative(n = 362)
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p y
GeparTrio Trial: Conclusions
Adapting neoadjuvant chemotherapy based on earlyresponse significantly improved DFS and OS vsconventional chemotherapy
Response-guided chemotherapy most effective in patientswith luminal A or luminal B tumors
Low pCR rates in these tumors
pCR not prognostic
No DFS benefit with response-guided chemotherapy inpatients with HER2-positive or triple-negative tumors
Von Minckwitz G, et al. SABCS 2011. Abstract S3-2.
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Prognosis and Prediction
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p y
DCIS Score: Determining Risk of
Recurrence After DCIS Resection DCIS Score: gene-based score designed to predict for local
recurrence[1]
Developed using subset of genes prognostic in both tamoxifen-treated and tamoxifen-untreated patients
Proliferation group: Ki67, STK15, survivin, CCNB1 (cyclin B1), MYBL2
Hormone receptor group: PgR
GSTM1
Reference group:ACTB (-actin), GAPDH, RPLPO, GUS, TFRC
Evaluated using samples and data from ECOG E5194 trial[2]
1. Solin LJ, et al. SABCS 2011. Abstract S4-6. 2. Hughes LL, et al. J Clin Oncol. 2009;27:5319-5324.
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y
DCIS Score: Patient Characteristics
(N = 327) Median age: 61 yrs
Postmenopausal: 76%
Median tumor size: 7 mm
Tumor size 10 mm: 80%
Negative margins 5 mm: 65%
ER positive: 97%
Treated with tamoxifen: 29% E5194 cohort 1 (low-/intermediate-grade DCIS, size
2.5 cm): 83%
E5194 cohort 2 (high-grade DCIS, size 1 cm): 17%
Solin LJ, et al. SABCS 2011. Abstract S4-6.
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DCIS Score: Risk of Ipsilateral Breast
Events (IBE)
Solin LJ, et al. SABCS 2011. Abstract S4-6.
Factor HR (95% CI) PValue
DCIS Score 2.34 (1.15-4.59) .02
21-gene RS 0.70 (0.15-2.65) .62
Tamoxifen use 0.56 (0.24-1.15) .12
10-Yr IBE by Risk Group
Yrs
5045403530
2520151050
0 2 4 6 8 10
Log-rank P= .02
DCIS Score GroupHighIntermediateLow
n
3645246
10-Yr Risk, % (95% CI)
27.3 (15.2-45.9)24.5 (13.8-41.1)12.0 (8.1-17.6)
Yrs
5045403530
25201510
50
0 2 4 6 8 10
Log-rank P= .01
DCIS Score GroupHighIntermediateLow
n
3645
246
10-Yr Risk, % (95% CI)
19.1 (9.0-37.7)8.9 (2.9-25.8)5.1 (2.8-9.5)
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DCIS Score: Conclusions
DCIS Score predicts 10-yr risk of IBE in patients with DCIStreated with surgery in the absence of radiation therapy
Not affected by adjuvant tamoxifen
Independent prognostic information on IBE risk providedabove that attained with clinical and pathologic variables
Solin LJ, et al. SABCS 2011. Abstract S4-6.
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