1. Phase III Investigation of Neoadjuvant Carboplatin ± Veliparib in Combination With Chemotherapy in Early-Stage TNBC
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
TNBC, triple-negative breast cancer.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. Neoadjuvant Chemotherapy + Carboplatin ± Veliparib for Early TNBC: Background
Achieving pCR with neoadjuvant therapy correlates with improved EFS and OS in TNBC vs pts with residual disease[1]
Veliparib: potent, orally available PARP 1/2 inhibitor
Preclinical evidence for increasing chemotherapy antitumor activity[2]
I-SPY2 pilot study suggested high probability for successful phase III trial of veliparib + carboplatin added to weekly T  AC as neoadjuvant therapy in TNBC[3]
Current phase III study evaluated addition of carboplatin ± veliparib to neoadjuvant T  AC in early stage TNBC, with particular interest in veliparib contribution to increased pCR rate[4]
AC, doxorubicin/cyclophosphamide; EFS, event-free survival; pCR, pathologic CR; T, paclitaxel; TNBC, triple-negative breast cancer.
1. Cortazar P, et al. Lancet. 2014;384: Donowho CK, et al. Clin Cancer Res. 2007;13: Rugo HS, et al. N Engl J Med. 2016;375: Geyer CE, et al. ASCO Abstract 520.
Slide credit: clinicaloptions.com

3. Neoadjuvant Chemotherapy + Carboplatin ± Veliparib for Early TNBC: Phase III Study Design
Stratified by BRCA status (mut vs no mut vs unknown), node stage (N0 vs N1-2), AC schedule (Q2W vs Q3W)
12 weeks
Veliparib + Carboplatin + Paclitaxel
(n = 316)
Previously untreated women with resectable
stage II-IIIA TNBC with documented gBRCA testing
(N = 634)
Doxorubicin +
Cyclophosphamide
(4 cycles)
Placebo + Carboplatin + Paclitaxel
(n = 160)
Surgery
Placebo + Placebo + Paclitaxel
(n = 158)
Veliparib 50 mg PO BID; carboplatin AUC 6 mg/mL Q3W; paclitaxel 80 mg/m2 Q1W.
AUC, area under the concentration curve; BCS, breast conserving surgery; EFS, event-free survival; gBRCA, germline BRCA; mut, mutation; MRD, minimal residual disease; pCR, pathologic CR; QoL, quality of life; TNBC, triple-negative breast cancer.
Primary objectives: pCR in breast and ipsilateral axillary nodes (ypT0/Tis, pN0)
Secondary objectives: conversion to BCS eligibility, EFS, OS, safety
Tertiary objectives: clinical response rate at Wk 12, pCR + MRD, QoL
Slide credit: clinicaloptions.com
Geyer CE, et al. ASCO Abstract 520.

4. Veliparib + Carboplatin + T  AC
Neoadjuvant Chemotherapy + Carboplatin ± Veliparib for Early TNBC: Pt Characteristics
Characteristic
Veliparib + Carboplatin + T  AC
(n = 316)
Carboplatin + T  AC
(n = 160)
T  AC
(n = 158)
Median age (range), yrs
> 50 yrs, %
51.0 (26-79)
52.2
49.0 (23-76)
45.6
50.0 (22-75)
48.7
Deleterious gBRCA mutation, %
14.2
15.6
14.6
Tumor stage, % T1 T2
T3-T4a
11.7
72.5
15.8
12.5
66.9
20.6
9.5
74.1
16.5
Lymph node stage N0/N1-N2, %
57.0/43.0
57.5/42.5
59.5/40.5
Planned AC schedule Q2W/Q3W, %
54.7/44.3
55.0/43.8
56.3/43.7
Longest tumor diameter > 30 mm, %
54.1
55.6
50.0
AC, doxorubicin/cyclophosphamide; gBRCA, germline BRCA; T, paclitaxel; TNBC, triple-negative breast cancer.
Slide credit: clinicaloptions.com
Geyer CE, et al. ASCO Abstract 520.

5. Rate of Clinical Response
Neoadjuvant Chemotherapy + Carboplatin ± Veliparib for Early TNBC: Efficacy
pCR
Rate of Intent for BCS
P = .139
P < .001
100
100
P = .132
P = .357 75 75
Pts (%) 50
Pts (%) 50 25 25
53.2
57.5
31.0
61.6
44.1
44.1
V + Cb + T → AC (n = 316)
Cb + T → AC (n = 160)
T → AC (n = 158)
V + Cb + T → AC (n = 73)
Cb + T → AC (n = 34)
T → AC (n = 34)
Rate of Clinical Response
Rate of MRD
P < .001
P < .001
P = .961
100
100
P = .739
AC, doxorubicin/cyclophosphamide; BCS, breast conserving surgery; Cb, carboplatin; MRD, minimal residual disease; pCR, pathologic CR; T, paclitaxel; TNBC, triple-negative breast cancer; V, veliparib. 75 75
Pts (%) 50
Pts (%) 50 25 25
83.4
83.3
55.7
68.3
70.0
47.2
V + Cb + T → AC (n = 316)
Cb + T → AC (n = 160)
T → AC (n = 158)
V + Cb + T → AC (n = 268)
Cb + T → AC (n = 140)
T → AC (n = 125)
Slide credit: clinicaloptions.com
Geyer CE, et al. ASCO Abstract 520. Reproduced with permission.

6. Neoadjuvant Chemotherapy + Carboplatin ± Veliparib for Early TNBC: pCR by Subgroup
Favors Cb + T → AC
Favors V + Cb + T → AC
Favors T → AC
Favors V + Cb + T → AC
Risk Difference (95% CI)
Risk Difference (95% CI)
All Pts
-4.34 (-13.8 to 5.1)
All Pts
22.15 (13.1 to 31.2)
BRCA1 and/or BRCA2 mutation
6.52 (-18.1 to 31.1)
BRCA1 and/or BRCA2 mutation
15.61 (-9.4 to 40.7)
No mutation in BRCA1 or BRCA2
-6.23 (-16.4 to 4.0)
No mutation in BRCA1 or BRCA2
23.18 (13.5 to 32.9) N0
-1.15 (-13.7 to 11.4) N0
27.96 (15.8 to 40.2)
Lymph node stage
Lymph node stage
N1-2
-8.39 (-22.5 to 5.7)
N1-2
15.09 (1.7 to 28.5)
AC, doxorubicin/cyclophosphamide; Cb, carboplatin; pCR, pathologic CR; T, paclitaxel; TNBC, triple-negative breast cancer; V, veliparib.
Q2W
-0.50 (-13.2 to 12.2)
Q2W
25.00 (12.9 to 37.1)
AC dose
AC dose
Q3W
-9.15 (-23.3 to 5.0)
Q3W
18.57 (4.9 to 32.2)
-50
-40
-30
-20
-10 10 20 30 40 50
-50
-40
-30
-20
-10 10 20 30 40 50
Risk Difference (95% CI)
Risk Difference (95% CI)
Slide credit: clinicaloptions.com
Geyer CE, et al. ASCO Abstract 520. Reproduced with permission.

7. Veliparib + Carboplatin + T  AC
Neoadjuvant Chemotherapy + Carboplatin ± Veliparib for Early TNBC: TEAEs
TEAE, %
Veliparib + Carboplatin + T  AC
(n = 313)
Carboplatin + T  AC
(n = 158)
T  AC
(n = 157)
Any grade 3/4
85.9
84.8
45.2
Any serious
30.4
26.6
14.0
AE leading to discontinuation of
Veliparib/placebo
Carboplatin/placebo
Paclitaxel
5.8
5.4
11.5
5.7
6.3
7.0
2.5
0.6
Fatal AE
0.3
Deaths, including non-tx related
2.9
AC, doxorubicin/cyclophosphamide; AE, adverse event; T, paclitaxel; TEAE, treatment-emergent adverse event; TNBC, triple-negative breast cancer; tx, treatment.
Higher incidence of hematologic and gastrointestinal AEs with carboplatin
No increase in sensory neuropathy seen with carboplatin
Slide credit: clinicaloptions.com
Geyer CE, et al. ASCO Abstract 520.

8. Veliparib + Carboplatin +
Neoadjuvant Chemotherapy + Carboplatin ± Veliparib for Early TNBC: TEAEs
TEAE in ≥ 10% of
pts in any arm during T tx segment, %
Veliparib + Carboplatin +
T  AC (n = 313)
Carboplatin +
T  AC (n = 158)
T  AC
(n = 157)
Any Grade
Grade 3/4
Neutropenia
70.0
57.2
61.4
53.2
9.5
2.5
Anemia
61.0
24.6
69.6
17.1
10.8
Thrombocytopenia
47.9
10.5
37.3
6.3
Leukopenia
12.8
4.2
15.9
5.1
3.8
0.6
Nausea
60.4
1.3
62.0
28.7
Diarrhea
32.3
1.9
26.0
26.1
Vomiting
20.1
28.4
Stomatitis
19.5
14.6
Fatigue
51.8
52.6
42.7
Peripheral neuropathy
37.7
1.0
40.5
40.1
Myalgia
18.5
16.5
17.8
Arthralgia
10.2
10.1
Heme GI
AC, doxorubicin/cyclophosphamide; GI, gastrointestinal; Heme, hematologic; T, paclitaxel; TEAE, treatment-emergent adverse event; TNBC, triple-negative breast cancer; tx, treatment.
Other
Geyer CE, et al. ASCO Abstract 520.

9. Neoadjuvant Chemotherapy + Carboplatin ± Veliparib for Early TNBC: Conclusions
Veliparib + carboplatin + T  AC significantly increased pCR rate over T  AC alone (53.2% vs 31.0%; P < .0001)
Addition of veliparib did not increase pCR rate over carboplatin + T  AC (53.2% vs 57.5%; P = .36)
pCR improvement likely due to carboplatin, without additional benefit with veliparib
Some toxicities, including hematologic and GI, increased with carboplatin addition
Carboplatin use increased T dose reductions and administration time
AC, doxorubicin/cyclophosphamide; GI, gastrointestinal; pCR, pathologic CR; T, paclitaxel; TEAE, treatment-emergent adverse event; TNBC, triple-negative breast cancer.
Slide credit: clinicaloptions.com
Geyer CE, et al. ASCO Abstract 520.

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