1. Phase III PlanB Final Analysis: Adjuvant TC vs ECT in Pts With High-Risk HER2-Negative Early Breast Cancer
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
ECT, epirubicin/cyclophosphamide followed by docetaxel; TC, docetaxel/cyclophosphamide.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. Adjuvant TC vs ECT in High-Risk HER2-Negative Early Breast Cancer: Background
Role of anthracycline-containing regimens for pts with early BC still debated
EBCTCG meta-analysis: reduced BC mortality with anthracycline + taxane regimens, increased cardiac mortality with anthracyclines[1]
USOR 9735: superior DFS and OS with TC x 4 vs AC x 4[2]
ABC joint analysis: improved iDFS with taxane + AC regimens vs TC x 6[3]
PlanB: prospective, randomized, open-label phase III trial of TC vs ECT in HER2-negative pts with early BC
Current analysis reports final 5-yr results[4]
AC, doxorubicin/cyclophosphamide; BC, breast cancer; ECT, epirubicin/cyclophosphamide followed by docetaxel; iDFS, invasive disease-free survival; TC, docetaxel/cyclophosphamide.
References:
1. EBCTCG, et al. Lancet. 2012;379:
2. Jones S, et al. J Clin Oncol. 2009;27:
3. Blum JL, et al. J Clin Oncol. 2017;[Epub ahead of print].
4. Harbeck N, et al. ASCO Abstract 504.
Slide credit: clinicaloptions.com
References in slidenotes.

3. PlanB: Study Design Primary endpoint: DFS, noninferiority margin: 4.4%
6 x Docetaxel 75 mg/m² + Cyclophosphamide 600 mg/m²
(n = 1222)
Pts ≤ 75 yrs of age with pN+ or high-risk* pN0 HER2­-negative EBC
(N = 2449)†
4 x Epirubicin 90 mg/m² + Cyclophosphamide 600 mg/m² 
4 x Docetaxel 100 mg/m²
(n = 1227)
All agents given IV Day 1 Q3W. RT per national guidelines.
*High-risk disease included those with pT ≥ 2, grade 2-3, uPA/PAI-1 high, HR-, or young age (≤ 35 yrs of age).
†In protocol amendment after 263 pts enrolled, HR+ pts with 0-3 LN and RS ≤ 11 excluded from randomization, given endocrine therapy per national guidelines. HR+ pts with 0-3 LN and RS > 11 or ≥ 4 LN randomized per original trial design.
Primary endpoint: DFS, noninferiority margin: 4.4%
Secondary endpoints: safety, OS
Translational subprotocol: prognostic impact of RS vs clinicopathology, outcome in pts with RS ≤ 11 treated with endocrine therapy
EBC, early breast cancer; HR, hormone receptor; LN, lymph node; RS, recurrence score; RT, radiation.
Slide credit: clinicaloptions.com
Harbeck N, et al. ASCO Abstract 504.

4. PlanB: Baseline Characteristics
Characteristic, n (%) TC
(n = 1222)
ECT
(n = 1227)
Premenopausal
439 (39.2)
429 (37.8) pN 1 2 3
727 (59.5)
404 (33.1)
72 (5.9)
19 (1.6)
714 (58.2)
428 (34.9)
63 (5.1)
22 (1.8) pT 4
637 (52.3)
532 (43.6)
41 (3.4)
9 (0.7)
705 (57.6)
471 (38.4)
42 (3.4)
7 (0.6)
Grade
1-2 (central)
1-2 (local)
3 (central)
3 (local)
659 (56.0)
782 (64.2)
518 (44.0)
437 (35.8)
664 (56.3)
787 (64.2)
516 (43.7)
438 (35.8)
Characteristic, n (%) TC
(n = 1222)
ECT
(n = 1227)
Surgery
BCS
Mastectomy
995 (81.6)
224 (18.4)
990 (80.8)
235 (19.2)
Triple negative (central)
214 (18.9)
211 (18.7)
HR+ (local)
1005 (82.2)
999 (81.4)
Recurrence score (HR+)
≤ 25
> 25
703 (72.5)
266 (27.5)
710 (73.8)
252 (26.2)
Ki-67 (central, semiquantitative)
0-10
15-35
≥ 40
364 (33.5)
567 (52.1)
157 (14.4)
384 (35.4)
560 (51.6)
141 (13.0)
BCS, breast-conserving surgery; ECT, epirubicin/cyclophosphamide followed by docetaxel; HR, hormone receptor; TC, docetaxel/cyclophosphamide.
Data missing for some subgroups; discordance between local/central labs.
Slide credit: clinicaloptions.com
Harbeck N, et al. ASCO Abstract 504.

5. PlanB: DFS HR
Subgroup
All pts
Recurrence score ≤ 25
Recurrence score > 25
pN0
pN1
pN2/3 Ki Ki
Ki-67 > 40
Local grade 1/2
Local grade 3
Central grade 1/2
Central grade 3
Triple negative
Mos
DFS (%)
HR: 0.996
(95% CI: )
Pts at Risk, n
TC 90
ECT 90
5-Yr DFS, %
100 80 60 40 20 12 24 36 48 72
TC ECT
25 32
DFS, disease-free survival; ECT, epirubicin/cyclophosphamide followed by docetaxel; TC, docetaxel/cyclophosphamide.
Difference in DFS within margin of noninferiority from original trial design
0.1
1.0 10
Favors TC
Favors ECT
Slide credit: clinicaloptions.com
Harbeck N, et al. ASCO Abstract 504. Reproduced with permission.

6. PlanB: DFS by Recurrence Score (HR+)
Mos
DFS (%)
Pts at Risk, n
TC 94
ECT 95
5-Yr DFS, %
100 80 60 40 20 12 24 36 48 72
TC ECT
19 21
Mos
DFS (%)
Pts at Risk, n
TC 86
ECT 85
5-Yr DFS, %
100 80 60 40 20 12 24 36 48 72
TC ECT
1 5
DFS, disease-free survival; ECT, epirubicin/cyclophosphamide followed by docetaxel; HR, hormone receptor; ITT, intent to treat; TC, docetaxel/cyclophosphamide.
Analysis in ITT pts with RS measurement after early protocol amendment
Slide credit: clinicaloptions.com
Harbeck N, et al. ASCO Abstract 504. Reproduced with permission.

7. PlanB: DFS Multivariable Analysis (HR+)
Factor HR
95% LCL
95% UCL
P Value
Recurrence score*
1.96
1.27
3.02
.002
pN1-3 vs pN0
1.64
1.13
2.38
.009
pN3 vs pN0-2
3.90
1.97
7.71
.0001
Local grade 3 vs 1/2
1.62
1.09
2.43
.018
Central grade 3 vs 1/2
1.49
0.97
2.28
.070
Ki-67 (semiquantitative)*
1.60
1.04
2.46
.034
Mastectomy vs BCS
1.87
1.26
2.77
BCS, breast-conserving surgery; DFS, disease-free survival; HR, hormone receptor; LCL, lower confidence limit; UCL, upper confidence limit.
*Fractionally ranked (75th to 25th percentile).
Analysis in pts receiving chemotherapy
Variables excluded from model: chemotherapy arm, age, pN2/3 vs pN0/1, tumor stage
Slide credit: clinicaloptions.com
Harbeck N, et al. ASCO Abstract 504.

8. PlanB: OS 100 80 60 OS (%) 40 5-Yr OS, % TC 95 ECT 95 HR: 0.94
(95% CI: ) 20
ECT, epirubicin/cyclophosphamide followed by docetaxel; TC, docetaxel/cyclophosphamide. 12 24 36 48 60 72
Mos
Pts at Risk, n
TC ECT
16 25
Slide credit: clinicaloptions.com
Harbeck N, et al. ASCO Abstract 504. Reproduced with permission.

9. PlanB: Safety Tx-related deaths (P = .2):
Grade 3/4 AE of Interest, n (%)
TC (n = 1178)
ECT (n = 1167)
P Value
Leukopenia
598 (50.8)
671 (57.5)
.001
Neutropenia
676 (57.9)
Febrile neutropenia
63 (5.3)
45 (3.9)
.09
Infection
82 (7.0)
62 (5.3) .1
Nausea
20 (1.7)
44 (3.8)
.002
Vomiting
5 (0.4)
23 (2.0)
< .001
Peripheral polyneuropathy
10 (0.8)
26 (2.2)
.007
HFS/palmar syndrome
9 (0.8)
33 (2.8)
Diarrhea
37 (3.1)
39 (3.3) .8
Mucositis/stomatitis
43 (3.7)
.003
Arthralgia/myalgia
18 (1.5)
35 (3.0)
.02
Pain
61 (5.2)
.01
Cardiac failure
3 (0.3)
1.0
Fatigue
68 (5.8)
Tx-related deaths (P = .2):
TC: 5 (0.4%)
ECT: 1 (0.1%)
Due to infectious complications (n = 5); pulmonary embolism (n = 1)
Dose reductions (P < .001):
TC: 78 (6.6%)
ECT: 230 (19.7%)
Cycle delays > 7 days (P = .004)
TC: 47 (4.0%)
ECT: 78 (6.7%)
AE, adverse event; ECT, epirubicin/cyclophosphamide followed by docetaxel; HFS, hand–foot syndrome; TC, docetaxel/cyclophosphamide; Tx, treatment.
Slide credit: clinicaloptions.com
Harbeck N, et al. ASCO Abstract 504.

10. PlanB: Conclusions
In pts with clinically high-risk or genomically intermediate-/high-risk HER2- negative early BC, TC noninferior to ECT for DFS
Similar 5-yr DFS and OS for TC vs ECT
No subgroup-specific benefit with anthracycline-containing ECT
Fewer grade 3/4 AEs, dose reductions/cycle delays with TC vs ECT
Study investigators conclude 6 x TC represents effective CT option for HER2-negative early BC, evaluation of novel therapeutics needed in subgroup of pts with high-RS tumors
Potential overtreatment with CT suggested by prolonged 5-yr DFS in intermediate-RS tumors to be addressed in WSG-ADAPT trial
AE, adverse event; BC, breast cancer; CT, chemotherapy; DFS, disease-free survival; ECT, epirubicin/cyclophosphamide followed by docetaxel; TC, docetaxel/cyclophosphamide; RS, recurrence score.
Slide credit: clinicaloptions.com
Harbeck N, et al. ASCO Abstract 504.

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