CCO Breast Cancer Dec 2011 EBC CME Slides

An Update on Early Breast Cancer
CCO Independent Conference Coverage

of the 2011 Annual Meeting of the AACR-CTRC San Antonio Breast Cancer Symposium*
December 6-10, 2011 San Antonio, Texas
*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 This program is supported by educational grants from

clinicaloptions.com/oncology
About These Slides

In the following slides, you will find highlights of the key studies from this meeting. Be sure to review the slide notes field for each slide for insightful commentary from our expert faculty
Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com)
Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing 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.

Faculty
Joyce OShaughnessy, MD
Co-Director, Breast Cancer Research Baylor Charles A. Sammons Cancer Center Texas Oncology US Oncology Dallas, Texas
Peter Ravdin, MD, PhD
Director of the Breast Cancer Program The University of Texas Health Science Center at San Antonio San Antonio, Texas

Disclosures
Joyce OShaughnessy, MD, has disclosed that she has received consulting fees from Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Caris Diagnostics, Eisai, Genentech, GlaxoSmithKline, GTx, Johnson & Johnson, Roche, and sanofi-aventis and fees for non-CME services from Bristol-Myers Squibb, Celgene, and sanofi-aventis. Peter Ravdin, MD, PhD, has disclosed that he has an ownership interest in Adjuvant, Inc.

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
Adjuvant Therapy

TEACH: Study Design

Primary endpoint: DFS Secondary endpoints: OS, recurrence-free survival, distant recurrence-free survival
Stratified by time from diagnosis, lymph node involvement, hormone receptor status Yr 1
Women with resected HER2-positive stage I-IIIc primary breast cancer and no previous trastuzumab therapy (N = 3147)
Goss P, et al. SABCS 2011. Abstract S4-7.
Lapatinib 1500 mg once daily (n = 1571)
Placebo (n = 1576)

TEACH: Risk of Recurrence in Patients Without Anti-HER2 Therapy

1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0
Yr(s) 1 2 3 4 5 6 7 8 9 10 96 Disease-Free Patients, % 99.9 96.7 93.1 91.0 87.8 84.4 81.1 79.2 77.2 74.9
Proportion of Patients With DFS
5 Yrs
10
Patients at Risk, n Placebo 1576 1569 1504 1430 1323 1043 781 539 310 181

TEACH: DFS and OS

DFS With Lapatinib vs Placebo Overall population Time since diagnosis < 1 yr 4 yrs > 4 yrs Hormone receptor status, % ER and/or PgR positive ER and PgR negative Lymph node involvement Positive Negative 1753 1394 0.86 (0.69-1.07) 0.78 (0.57-1.07) 1859 1288 0.98 (0.77-1.25) 0.68 (0.52-0.89) .886 .006 647 2248 899 0.70 (0.50-0.99) 0.84 (0.69-1.03) 0.81 (0.52-1.26) Patients, n 3147 HR (95% CI) 0.83 (0.70-1.00) P Value .053
No improvement in OS demonstrated with use of lapatinib: HR: 0.99 (95% CI: 0.74-1.31; P = .966)

TEACH: DFS in Patients With Centrally Confirmed HER2+ Disease

Outcome All DFS events Local Regional Distant CNS recurrence Contralateral breast Second primary malignancy Lapatinib,% (n = 1230) 13 2 2 8 <1 <1 2 Placebo,% (n = 1260) 17 3 2 11 2 1 2 0.66 (0.33-1.34) .286 DFS HR (95% CI) 0.82 (0.67-1.00) P Value .04

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%)
Adverse Events, % Lapatinib (n = 1573) Grade 1/2 Diarrhea Rash Nausea Fatigue 55 54 17 15 Grade 3/4 6 6 1 1 16 15 11 13 Placebo (n = 1574) Grade 1/2 Grade 3/4 1 1 1 1

TEACH: Conclusions
Adjuvant lapatinib after resection of early HER2+ breast cancer failed to 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


ABCSG-12: Study Design

Key endpoints
Primary: DFS at 5 yrs Secondary: relapse-free survival, OS, bone mineral density, safety
1803 premenopausal patients with breast cancer, stage I/II (goserelin 3.6 mg/ 28 days) Stratified by: ER+ and/or PgR+ Age Stage Grade Lymph nodes
TAM 20 mg/day ANA 1 mg/day R TAM + ZOL 4 mg q6m ANA + ZOL 4 mg q6m Treatment 3 yrs (median follow-up: 48 mos)
Long-term monitoring for 5 yrs for recurrence and survival (DFS, OS)
3-yr BMD
5-yr BMD
Gnant M, et al. N Engl J Med. 2009;360:679-691.

ABCSG-12 (84 Mos): Efficacy

DFS
100 80 Univariate DFS (%) 60 40 20 0 0 12 24 Events, HR P n (95% CI) Value No 132/903 ZOL ZOL 98/900 vs no ZOL (Logrank) Multiple Cox Regression HR (95% CI) vs no ZOL 0.71 (0.55-0.92) 84 96 .011 0 108 0 12 24 P Value 100 80 Univariate OS (%) 60 40 20 Events, HR P n (95% CI) Value No 49/903 ZOL ZOL 33/900 vs no ZOL (Mantel -Cox) Multiple Cox Regression HR (95% CI) vs no ZOL 0.61 (0.39-0.96) 84 96 .033 108 P Value
OS
0.72 .014 (0.56-0.94) 48 60 72
0.63 .049 (0.40-0.99) 48 60 72
36
36
Mos Since Randomization Pts at Risk, n No ZOL 903 858 ZOL 900 862 833 841 807 822 758 788 653 674 521 544 405 419 191 208 Pts at Risk, n 864 No ZOL 903 868 ZOL 900 856 858
Mos Since Randomization 839 849 811 818 706 708 576 587 456 454 215 232
Gnant M, et al. SABCS 2011. Abstract S1-2

ABCSG-12 (84 Mos): First DFS Events

140 120 First Event/Patient (n) 100 80 60 40 20 0 36 No ZOL (n = 903) 65 56 3 18 13 14 11 Death without previous recurrence Secondary malignancy Contralateral breast cancer Distant recurrence Locoregional recurrence
19 ZOL (n = 900)
Gnant M, et al. SABCS 2011. Abstract S1-2

ABCSG-12 (84 Mos): Age Effect on DFS

40 Yrs of Age or Younger
100 80 DFS (%) 60 40 20 0
No ZOL 42/213 ZOL 35/200 Univariate Events, n HR (95% CI) vs no ZOL 0.87 (0.55-1.36) P Value (Log-rank) .525
Older Than 40 Yrs of Age

100 80 60 40
Events, n Univariate HR (95% CI) vs no ZOL 0.66 (0.48-0.92) P Value (Log-rank) .013
20 0
No ZOL 90/690 ZOL 63/700
12
24
36
48
60
72
84
96 108
12
24
36
48
60
72
84
96 108
Mos Since Randomization

Pts at Risk, n No ZOL213 202 ZOL 200 192 194 185 189 180 177 169 157 148 127 125 102 94 52 48 Pts at Risk, n No ZOL 690 656 ZOL 700 670
Mos Since Randomization

639 656 616 642 581 619 496 526 394 419 303 325 139 160
Gnant M, et al. SABCS 2011. Abstract S1-2.

ABCSG-12: Conclusions
Survival benefits with addition of ZOL to endocrine therapy first reported at median follow-up of 48 mos are still present at 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.

ZO-FAST: 5-Yr Final Analysis

Treatment duration 5 yrs
Stage I-IIIa breast cancer

Postmenopausal or amenorrheic due to cancer treatment ER+ and/or PgR+ T-score -2 SD N = 1065
Letrozole + Zoledronic Acid 4 mg q6m
Letrozole + Delayed* Zoledronic Acid 4 mg q6m *If 1 of the following occurs:

BMD T score < -2 SD Clinical fracture Asymptomatic fracture at 36 mos
De Boer R, et al. SABCS 2011. Abstract S1-3.

ZO-FAST (Primary Endpoint): Median Change in Lumbar Spine BMD

6 Change in LS (LS-L4) BMD (%) 4 339 2 0 -2 369 -4 -6 12 mos 343 24 mos 311 36 mos 294 48 mos 264 60 mos 360 5.9% 8.2% 8.8% 9.2% 10.0% 313 Immediate ZOL Delayed ZOL P < .0001 for each 290 264

ZO-FAST: Final 5-Yr DFS

100 90 80 70 DFS (%) 60 50 40 30 20 10 0 6 12 18 24 30 36 42 48 54 60 66 Time on Study (Mos) Pts at Risk, n 518 500 488 475 376 IM-ZOL 532 511 491 475 463 368 D-ZOL 533
*Censored patients at initiation of delayed ZOL (n = 144).
100 90 ITT Population DFS (%) 80 70 60 50 40 30 20 10 0 0 6 12 18 24 30 36 42 48 54 60 66 Time on Study (Mos) Pts at Risk, n IM-ZOL 532 518 500 488 475 376 D-ZOL 533 459 402 376 350 267 0 HR: 0.62; log-rank P = .024 IM-ZOL 4 mg (42 events) D-ZOL 4 mg (53 events) Censored Analysis*
HR: 0.66; log-rank P = .0375 IM-ZOL 4 mg (42 events) D-ZOL 4 mg (62 events)

ZO-FAST: Disease Recurrence

Disease Recurrence 70 60 Patients (n) 50 40 30 20 10 0 29 6 12 D-ZOL (n = 533) 3 5 IM-ZOL (n = 532) 41 Distant Contralateral Local Patients (n) 70 60 50 40 30 20 10 0 24 D-ZOL (n = 533) 9 11 11 9 9 5 14 IM-ZOL (n = 532) Key Sites of Distant Recurrence* Liver Lung Lymph node Bone
*Multiple sites may be recorded within the same patient. De Boer R, et al. SABCS 2011. Abstract S1-3.

ZO-FAST: Overall Survival (ITT Population)

100 90 80 70 OS (%) 60 50 40 30 20 10 0 0 Pts at Risk, n IM-ZOL 532 D-ZOL 533 6 12 522 519 18 24 30 36 42 Time on Study (Mos) 511 502 505 491 48 485 480 54 60 406 407 66 HR: 0.69; log-rank P = .196 IM-ZOL 4 mg (26 events) D-ZOL 4 mg (36 events)

ZO-FAST: Conclusions
Immediate initiation of ZOL at start of letrozole significantly prolonged DFS vs delayed initiation of ZOL in postmenopausal 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 and subset 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.

Zoledronic Acid Studies: DFS Comparison

0.66 ZO-FAST[1]
104 events
N = 1065
P Value .0375
0.75 AZURE: > 5 yrs postmenopausal[2] 263 events ABCSG-12[3] 230 events
n = 1041
.02
0.71
N = 1803
.011
0.2
0.4
0.6
0.8 HR
1.0
1.2
1.4
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.

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
Stratified by age, number of positive nodes, and ER/PgR status Clodronate 1600 mg/day* (n = 1662) 3 Yrs
Women with stage I-III breast cancer (N = 3323)
Placebo* (n = 1661)
*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: Analysis of Specified Endpoints

Endpoint Events, n Clodronate (n = 1655) DFS OS RFI BMFI NBMFI 286 140 148 61 78 Placebo (n = 1656) 312 167 177 80 105 0.913 (0.778-1.072) 0.842 (0.672-1.054) 0.834 (0.671-1.038) 0.765 (0.548-1.068) 0.743 (0.554-0.996) .266 .131 .101 .114 .046 HR (95% CI) P Value
Paterson A, et al. SABCS 2011. Abstract S2-3.

NSABP B-34 Subset Analysis: DMFI, RFI, BMFI, NBMFI in Pts Aged > 50 Yrs
Endpoint for Patients Aged 50 Yrs or Older DMFI RFI BMFI NBMFI HR 0.62 0.76 0.61 0.63 P Value .003 .05 .024 .015
Paterson A, et al. SABCS 2011. Abstract S2-3.

NSABP B-34: Conclusions

No significant benefit in DFS (primary endpoint) with oral clodronate 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 with significant 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.

German GAIN Trial: Study Design

Randomized 2:1* Yr 2
Patients aged 65 yrs or younger with previously untreated node-positive primary breast cancer (N = 3023)
Ibandronate 50 mg/day PO (n = 2015)
Observation (n = 1008)
*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.

GAIN: Patient Characteristics

Characteristic Age, median yrs Premenopausal, % pT4, % pN1, % pN2, % pN3, % Mastectomy, % Ductal invasive, % Grade 3, % Hormone receptor positive, % HER2 positive, %
Ibandronate (n = 1996) 49 48.4 2.1 38.1 34.9 27.0 44.5 77.4 47.3 76.5 22.1
Observation (n = 998) 50 47.2 1.4 37.1 36.3 26.7 43.3 77.1 44.3 77.7 21.8

GAIN: DFS and OS (ITT)

Product-Limit Survival Estimates With Number of Subjects at Risk 1.0 0.8 Survival Probability 0.6 0.4 0.2 + Censored 1.0 0.8 0.6 0.4 0.2 Product-Limit Survival Estimates With Number of Subjects at Risk + Censored
3-yr DFS: Ibandronate 87.6% Observation: 87.2% Cox regression: HR: 0.945 (95% CI: 0.768-1.16; P = .59)
3-yr OS: Ibandronate 94.7% Observation: 94.1% Cox regression: HR: 1.04 (95% CI: 0.763-1.42; P = .80)
0 Pts at risk, n
1996 998
1814 871
1590 727
1057 483
555 264
210 105
0 Pts at risk, n
1996 998
1836 886
1653 756
1121 506
586 277
219 112
12
24
36 48 DFS (Mos)
60
12
24
36 48 OS (Mos)
60
Ibandronate Mobus V, et al. SABCS 2011. Abstract S2-4.
Observation

GAIN: Subgroup Analyses

DFS for Ibandronate in Subgroups
pN1 pN2 pN3 ER and/or PgR positive ER and PgR negative Pre- and perimenopausal Postmenopausal < 60 yrs 60 yrs 0.5 Better with ibandronate
Mobus V, et al. SABCS 2011. Abstract S2-4. 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)
1.0 HR
1.5 Worse with ibandronate

GAIN: Conclusions
Adjuvant ibandronate did not improve DFS nor OS following dose-dense chemotherapy in patients with node-positive primary breast cancer GAIN trial still ongoing to compare the 2 different dosedense chemotherapy regimens

Ongoing Phase III Trials of Antitumor Properties of Bone-Targeted Agents

Trial SWOG 0307 NATAN D-CARE HOBOE Regimen ZOL vs clodronate vs ibandronate ZOL after neoadjuvant chemo Dmab 120 mg/mo for 6 mos, then 120 mg q3m vs placebo Triptorelin + tamoxifen vs triptorelin + letrozole vs triptorelin + letrozole + ZOL FEC-D vs FEC-DG 2 yrs ZOL vs 5 yrs ZOL Dmab 60 mg q6m vs placebo Primary Outcomes DFS, OS EFS Bone metastasisfree survival DFS
SUCCESS ABCSG-18
DFS Time to first fracture
Neoadjuvant Therapy

GeparTrio Trial: Study Design

TAC-NX* (4 cycles NX) (n = 301) Not working? Try another type of chemotherapy Minimal response (n = 622)
TAC x 6 (4 additional cycles TAC) (n = 321)
Women with operable or locally advanced breast cancer (N = 2072)
TAC* (2 cycles)
Assess response
*TAC regimen: docetaxel 75 mg/m2, doxorubicin 50 mg/m2, CR or PR cyclophosphamide 500 mg/m2 all on Day 1 q21d. 2 NX regimen: vinorelbine 25 mg/m on Days 1 and 8, (n = 1390) 2 capecitabine 1000 mg/m on Days 1-14 q21d. Response assessed by ultrasound/palpation. Working? < 50% tumor reduction.
Give more of the same chemotherapy
Von Minckwitz G, et al. SABCS 2011. Abstract S3-2.

GeparTrio Trial: DFS and OS

Median follow-up: 62 mos
Endpoint DFS OS HR for Response-Guided vs Conventional Chemotherapy (95% CI) 0.71 (0.60-0.85) 0.79 (0.63-0.99) P Value < .001 .048
DFS benefit in early responding and nonresponding patients who received response-guided vs conventional chemotherapy
Patient Subgroup Responders Nonresponders Treatment Comparison TAC x 8 vs TAC x 6 TAC-NX vs TAC x 6 HR for DFS (95% CI) 0.78 (0.62-0.97) 0.59 (0.49-0.82) P Value .026 .001

GeparTrio Trial: DFS by Patient Subgroup

Subgroup N patients Overall 2012 Age (yrs) <40 353 40 1659 cT-stage cT1-3 1737 cT4 267 cT-size < 40 mm 775 40 mm 1212 cN status Negative 894 Positive NR Histological type Ductal or other 1571 Lobular 270 Grade 1 or 2 1176 3 725 Hormone receptor status Negative 717 Positive 1295 HER2 status Negative 1145 Positive 486 Breast cancer phenotype Luminal A 572 Luminal B (HER2-) 211 Luminal B (HER2+) 281 HER2+ (nonluminal) 178 Triple negative 362 0.2 0.4 0.6 0.8 1.0 1.2 1.4 Response-guided treatments better HR (95% CI) 0.74 (0.60-0.85) 0.66 (0.42-1.03) 0.73 (0.60-0.88) 0.70 (0.56-0.85) 0.79 (0.54-1.17) 0.62 (0.44-0.85) 0.79 (0.63-0.98) 0.84 (0.61-1.14) 0.66 (0.53-0.82) 0.73 (0.60-0.88) 0.61 (0.37-1.03) 0.79 (0.61-1.01) 0.65 (0.49-0.85) 0.94 (0.73-1.22) 0.56 (0.44-0.73) 0.63 (0.49-0.81) 0.72 (0.51-1.04) 0.55 (0.37-0.82) 0.40 (0.20-0.79) 0.56 (0.33-0.96) 1.01 (0.61-1.67) 0.87 (0.61-1.25) Conventional treatments better Test for Interaction 0.67 0.66 0.22 0.19 0.71 0.25 0.008 0.54 0.12-0.01

GeparTrio Trial: pCR by Breast Cancer Subtype

40 35 30 pCR (%) 25 20 15 10 5 0 Luminal A (n = 572) Luminal B (HER2-) (n = 211) Luminal B (HER2+) (n = 281) HER2+ Triple Negative (Nonluminal) (n = 362) (n = 178)

GeparTrio Trial: Conclusions

Adapting neoadjuvant chemotherapy based on early response significantly improved DFS and OS vs conventional chemotherapy Response-guided chemotherapy most effective in patients with luminal A or luminal B tumors
Low pCR rates in these tumors pCR not prognostic
No DFS benefit with response-guided chemotherapy in patients with HER2-positive or triple-negative tumors
Prognosis and Prediction

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 tamoxifentreated 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.

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.

DCIS Score: Risk of Ipsilateral Breast Events (IBE)

Factor DCIS Score 21-gene RS Tamoxifen use HR (95% CI) 2.34 (1.15-4.59) 0.70 (0.15-2.65) 0.56 (0.24-1.15) 10-Yr IBE by Risk Group
50 45 40 35 30 25 20 15 10 5 0
DCIS Score Group n High Intermediate 36 Low 45 246 Log-rank P = .02 10-Yr Risk, % (95% CI) 27.3 (15.2-45.9) 24.5 (13.8-41.1) 12.0 (8.1-17.6)
P Value .02 .62 .12
Yrs Solin LJ, et al. SABCS 2011. Abstract S4-6.
10
50 45 40 35 30 25 20 15 10 5 0
DCIS Score Group n High Intermediate 36 Low 45 246 Log-rank P = .01
10-Yr Risk, % (95% CI) 19.1 (9.0-37.7) 8.9 (2.9-25.8) 5.1 (2.8-9.5)
Yrs
10

DCIS Score: Conclusions

DCIS Score predicts 10-yr risk of IBE in patients with DCIS treated with surgery in the absence of radiation therapy
Not affected by adjuvant tamoxifen Independent prognostic information on IBE risk provided above that attained with clinical and pathologic variables
Solin LJ, et al. SABCS 2011. Abstract S4-6.
Go Online for More CCO Coverage of Breast Cancer!

Capsule Summaries of all the key data Expert Analysis of the key early-stage and metastatic breast cancer presentations as part of downloadable PowerPoint slides

CCO Breast Cancer Dec 2011 EBC CME Slides

Загружено:

Сведения о документе

Исходное описание:

Авторское право

Доступные форматы

Поделиться этим документом

Поделиться или встроить документ

Параметры публикации

Этот документ был вам полезен?

Это неприемлемый материал?

Авторское право:

Доступные форматы

CCO Breast Cancer Dec 2011 EBC CME Slides

Загружено:

Авторское право:

Доступные форматы

An Update on Early Breast Cancer

CCO Independent Conference Coverage

An Update on Early Breast Cancer

About These Slides

An Update on Early Breast Cancer

Peter Ravdin, MD, PhD

An Update on Early Breast Cancer

An Update on Early Breast Cancer

Overview of Early Breast Cancer

Prognosis and Prediction

An Update on Early Breast Cancer

TEACH: Study Design

Lapatinib 1500 mg once daily (n = 1571)

An Update on Early Breast Cancer

TEACH: Risk of Recurrence in Patients Without Anti-HER2 Therapy

Proportion of Patients With DFS

Goss P, et al. SABCS 2011. Abstract S4-7.

An Update on Early Breast Cancer

TEACH: DFS and OS

An Update on Early Breast Cancer

TEACH: DFS in Patients With Centrally Confirmed HER2+ Disease

Goss P, et al. SABCS 2011. Abstract S4-7.

An Update on Early Breast Cancer

Goss P, et al. SABCS 2011. Abstract S4-7.

An Update on Early Breast Cancer

DFS benefit with lapatinib observed in 2 patient subgroups

HER2 status reassessed by central review

Most common AEs associated with lapatinib: diarrhea and rash

An Update on Early Breast Cancer

ABCSG-12: Study Design

Gnant M, et al. N Engl J Med. 2009;360:679-691.

An Update on Early Breast Cancer

ABCSG-12 (84 Mos): Efficacy

0.72 .014 (0.56-0.94) 48 60 72

0.63 .049 (0.40-0.99) 48 60 72

Gnant M, et al. SABCS 2011. Abstract S1-2

An Update on Early Breast Cancer

ABCSG-12 (84 Mos): First DFS Events

Gnant M, et al. SABCS 2011. Abstract S1-2

An Update on Early Breast Cancer

ABCSG-12 (84 Mos): Age Effect on DFS

Older Than 40 Yrs of Age

No ZOL 90/690 ZOL 63/700

Mos Since Randomization

Mos Since Randomization

Gnant M, et al. SABCS 2011. Abstract S1-2.

An Update on Early Breast Cancer

An Update on Early Breast Cancer

ZO-FAST: 5-Yr Final Analysis

Stage I-IIIa breast cancer

Letrozole + Zoledronic Acid 4 mg q6m

Letrozole + Delayed* Zoledronic Acid 4 mg q6m *If 1 of the following occurs:

De Boer R, et al. SABCS 2011. Abstract S1-3.

An Update on Early Breast Cancer

ZO-FAST (Primary Endpoint): Median Change in Lumbar Spine BMD

De Boer R, et al. SABCS 2011. Abstract S1-3.

An Update on Early Breast Cancer

ZO-FAST: Final 5-Yr DFS

De Boer R, et al. SABCS 2011. Abstract S1-3.

An Update on Early Breast Cancer

ZO-FAST: Disease Recurrence

An Update on Early Breast Cancer

ZO-FAST: Overall Survival (ITT Population)