1. ABC Trials Joint Analysis: TC vs TaxAC in High-Risk, HER2-Negative Early Breast Cancer
CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016
*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.
ABC, anthracyclines in early breast cancer; TC, docetaxel/cyclophosphamide; TaxAC, anthracycline/taxane-based chemotherapy.
This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

2. ABC Joint Analysis of TC vs TaxAC in HER2- Breast Cancer: Background
2011 EBCTCG meta-analysis[1]
10-yr BC mortality similar with std doses of anthracyclines; reduced with higher cumulative doses of anthracyclines vs CMF
8-yr BC mortality further reduced by adding taxanes to anthracyclines (TaxAC)
10-yr BC mortality reduced by 1/3 with TaxAC vs no chemotherapy
Cardiac mortality increased with anthracyclines vs CMF or nil
USOR trial showed superior OS for TC vs AC (HR: 0.69; P = .032)[2]
Pooled analysis undertaken to determine if 6 cycles of TC is noninferior to TaxAC in women with resected, high-risk, HER2- negative breast cancer[3]
ABC, anthracyclines in early breast cancer; AC, doxorubicin/cyclophosphamide; CMF, cyclophosphamide/methotrexate/fluorouracil; EBCTCG; Early Breast Cancer Trialists' Collaborative Group; TC, docetaxel/cyclophosphamide; TaxAC, anthracycline/taxane-based chemotherapy.
1. EBCTCG, et al. Lancet. 2012;379: Jones S, et al. J Clin Oncol. 2009;27: Blum JL, et al. ASCO Abstract 1000.
Slide credit: clinicaloptions.com

3. TC vs TaxAC in HER2- Breast Cancer (ABC Joint Analysis): Timeline, Accrual, Tx
Data from 3 clinical trials of anthracyclines in early breast cancer (ABC trials) prospectively pooled for analysis
Pts received same general regimens across trials
TaxAC arms: concurrent TAC or sequential AC followed by paclitaxel (only in NSABP B-49)
Other arms: TC
ER+ or PgR+ pts: ≥ 5 yrs endocrine therapy
Trial
Accrual, n
Dates of Accrual
Median Follow-up, Yrs
USOR
1295
May June 2009
6.3
NASBP B-461 USOR 07132
1077
May Jan 2012
4.8
NSABP B-49
1870
April Nov 2013
2.2
ABC, anthracyclines in early breast cancer; AC, doxorubicin/cyclophosphamide; ER, estrogen receptor; PgR, progesterone receptor; TAC, docetaxel/doxorubicin/cyclophosphamide; TC, docetaxel/cyclophosphamide; TaxAC, anthracycline/taxane-based chemotherapy; Tx, treatment.
Slide credit: clinicaloptions.com
Blum JL, et al. ASCO Abstract 1000.

4. TC vs TaxAC in HER2- Breast Cancer: Eligibility Criteria
HER2-negative breast cancer
De novo disease
LVEF ≥ 50%
Node positive or high-risk node negative; pathology includes 1 of the following
pT1-3 if PN1, pN2a, pN3a, pN3b
pT2-3 if pN0
pT1c if pN0 and either:
ER and PgR negative
ER+ or PgR+ and either grade 3 or Oncotype DX recurrence score ≥ 31 (for USOR ) or ≥ 25 (for B-46I/07132 and B-49)
ER, estrogen receptor; LVEF, left ventricular ejection fraction; PgR, progesterone receptor; TC, docetaxel/cyclophosphamide; TaxAC, anthracycline/taxane-based chemotherapy;
Slide credit: clinicaloptions.com
Blum JL, et al. ASCO Abstract 1000.

5. TC vs TaxAC in HER2- Breast Cancer: Statistical Plan
Primary objective: determine if iDFS with TC noninferior to TaxAC
Inferiority predefined as HR ≥ 1.18 stratified by parent trial, nodal status, and hormone receptor status
Observed HR with 668 events would need to be significantly < 1.18 to establish noninferiority
1 interim analysis planned for futility at 334 iDFS events
Secondary objectives: RFI, OS, toxicity
Prespecified subset analyses
Cox models testing association between primary endpoint and stratification variables (parent trial, nodal status, ER/PgR positivity)
Tests for treatment by covariate interactions
Formal subgroup analyses if interactions significant at P < .01
ER, estrogen receptor; iDFS, invasive disease-free survival; PgR, progesterone receptor; RFI, recurrence-free interval; TC, docetaxel/cyclophosphamide; TaxAC, anthracycline/taxane-based chemotherapy.
Slide credit: clinicaloptions.com
Blum JL, et al. ASCO Abstract 1000.

6. TC vs TaxAC in HER2- Breast Cancer: Pt Characteristics
B-46I/07132 (N = 1051)
B-49 (N = 1819)
Total
(N = 4156)
Median follow-up, yrs
6.3
4.8
2.2
3.2
Age, %
≤ 49 yrs
50-59 yrs
≥ 60 yrs 37 26 38 35 27 31 34 36 29
White, % 88 83 84 85
Positive nodes, %
1-3
4-9
10+ 51 11 3 43 14 5 46 40 4 41 44
ER+ or PgR+, % 71 67 68 69
ER, estrogen receptor; PgR, progesterone receptor; TC, docetaxel/cyclophosphamide; TaxAC, anthracycline/taxane-based chemotherapy.
Slide credit: clinicaloptions.com
Blum JL, et al. ASCO Abstract 1000.

7. TC vs TaxAC in HER2- Breast Cancer: Interim Analysis
Data cutoff for interim analysis: October 31, 2015
399 of 668 iDFS events (59.7%) for definitive analysis reported
Interim analysis performed on initial 334 events reported
Observed HR for iDFS for TC vs TaxAC: 1.202, exceeding prespecified threshold for futility (> 1.18)
DMC recommended early reporting in accordance with statistical plan
All subsequent data reported based on 399 events reported by data cutoff
DMC, Data Monitoring Committee; HR, hazard ratio; iDFS, invasive disease-free survival; TC, docetaxel/cyclophosphamide; TaxAC, anthracycline/taxane-based chemotherapy.
Slide credit: clinicaloptions.com
Blum JL, et al. ASCO Abstract 1000.

8. TC vs TaxAC in HER2- Breast Cancer: Invasive DFS
4-yr iDFS: 88.2% for TC vs 90.7% for TaxAC
iDFS
HR for TC vs TaxAC (95% CI)
P Value
Overall
1.23 ( )
.04
Parent trial
USOR06-090
B-46I/07132
B-49
1.31 ( )
1.34 ( )
1.00 ( )
.57
Hormone status
Negative
Positive
1.42 ( )
1.12 ( )
.28
Number of nodes
1-3
4-9
10+
1.03 ( )
1.27 ( )
1.38 ( )
1.69 ( )
.15
iDFS, invasive disease-free survival; TC, docetaxel/cyclophosphamide; TaxAC, anthracycline/taxane-based chemotherapy.
Slide credit: clinicaloptions.com
Blum JL, et al. ASCO Abstract 1000.

9. TC vs TaxAC in HER2- Breast Cancer: iDFS Exploratory Analysis
4-Yr iDFS, %
4-Yr iDFS Delta, %
TaxAC AC
HR for TC vs TaxAC (95% CI)
P Value
Overall
90.7
88.2
2.5
1.23 ( )
.04
Positive nodes and ER/PgR negative
1-3 4+
89.5
85.5
71.8
87.0
74.6
60.8
10.9
11.0
1.31 ( )
1.58 ( )
1.34 ( )
.71
Positive nodes and ER or PgR positive
91.5
94.3
87.2
94.2
92.3
81.4
-2.7
2.0
5.8
0.69 ( )
1.14 ( )
1.46 ( )
.026
ER, estrogen receptor; PgR, progesterone receptor; iDFS, invasive disease-free survival; TC, docetaxel/cyclophosphamide; TaxAC, anthracycline/taxane-based chemotherapy
Slide credit: clinicaloptions.com
Blum JL, et al. ASCO Abstract 1000.

10. TC vs TaxAC in HER2- Breast Cancer: First iDFS Events
Type of Event TC
(n = 2094)
TaxAC
(n = 2062)
Total
(N = 4156)
Locoregional 46 34 80
Distant
110 75
185
Recurrence site unknown 19 12 31
CBC 3 6
Leukemia 5
Other 2nd primary 20 22 42
Death 28 50
CBC, contralateral breast cancer; iDFS, invasive disease-free survival; TC, docetaxel/cyclophosphamide; TaxAC, anthracycline/taxane-based chemotherapy
4-yr OS for TC vs TaxAC: 94.7% vs 95.0%
HR: 1.08 (95% CI: ; P = .60)
Slide credit: clinicaloptions.com
Blum JL, et al. ASCO Abstract 1000.

11. TC vs TaxAC in HER2- Breast Cancer: Conclusions
Treatment with TaxAC results in superior iDFS vs TC
iDFS HR for TC vs TaxAC: 1.202
Prespecified noninferiority boundary of 1.18 crossed, prompting early data reporting for futility
4-yr OS similar between groups (~ 95%)
Exploratory subgroup analyses suggest TaxAC provides:
Minimal or no benefit in ER+/node-negative pts
Small benefit in ER+/1-3 node-positive and ER-/node-negative pts
Large benefit in ER /≥ 4 node-positive and ER-/node-positive pts
Additional analysis needed to identify biomarkers associated with anthracycline benefit across this heterogeneous pt population
ER, estrogen receptor; iDFS, invasive disease-free survival; OS, overall survival; PgR, progesterone receptor; TC, docetaxel/cyclophosphamide; TaxAC, anthracycline/taxane-based chemotherapy
Slide credit: clinicaloptions.com
Blum JL, et al. ASCO Abstract 1000.

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