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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
Faculty
Joyce OShaughnessy, MD
Co-Director, Breast Cancer Research Baylor Charles A. Sammons Cancer Center Texas Oncology US Oncology Dallas, Texas
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.
Neoadjuvant Therapy
GeparTrio Trial : response-guided vs conventional chemotherapy
Adjuvant Therapy
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.
Placebo (n = 1576)
5 Yrs
10
Patients at Risk, n Placebo 1576 1569 1504 1430 1323 1043 781 539 310 181
No improvement in OS demonstrated with use of lapatinib: HR: 0.99 (95% CI: 0.74-1.31; P = .966)
Goss P, et al. SABCS 2011. Abstract S4-7.
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
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
OS
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
19 ZOL (n = 900)
20 0
12
24
36
48
60
72
84
96 108
12
24
36
48
60
72
84
96 108
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.
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)
*Multiple sites may be recorded within the same patient. De Boer R, et al. SABCS 2011. Abstract S1-3.
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.
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.
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 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
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]
Patients aged 65 yrs or younger with previously untreated node-positive primary breast cancer (N = 3023)
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.
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
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
Observation
1.0 HR
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
SUCCESS ABCSG-18
Neoadjuvant Therapy
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.
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
No DFS benefit with response-guided chemotherapy in patients with HER2-positive or triple-negative tumors
1. Solin LJ, et al. SABCS 2011. Abstract S4-6. 2. Hughes LL, et al. J Clin Oncol. 2009;27:5319-5324.
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.
10
50 45 40 35 30 25 20 15 10 5 0
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
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