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Clinical Trial Results:
A Randomized, Placebo-Controlled, Double-Blind, Phase 3 Study Evaluating Safety and Efficacy of the Addition of Veliparib Plus Carboplatin Versus the Addition of Carboplatin to Standard Neoadjuvant Chemotherapy Versus Standard Neoadjuvant Chemotherapy in Subjects With Early Stage Triple Negative Breast Cancer (TNBC)

Summary
EudraCT number	2013-002377-21
Trial protocol	BE DE CZ HU GB ES IT PL FR
Global end of trial date	12 Nov 2020

Results information
Results version number	v1(current)
This version publication date	29 Oct 2021
First version publication date	29 Oct 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

M14-011

ISRCTN number

US NCT number

NCT02032277

WHO universal trial number (UTN)

Sponsor organisation name

AbbVie

Sponsor organisation address

AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6 4UB

Public contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com

Scientific contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

12 Nov 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

12 Nov 2020

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study was to assess the rate of pathologic complete response (pCR) in breast and any resected lymph node tissue after treatment with neoadjuvant veliparib in combination with carboplatin and paclitaxel followed by doxorubicin + cyclophosphamide compared to two neoadjuvant chemotherapy regimens (carboplatin + paclitaxel followed by doxorubicin + cyclophosphamide or paclitaxel alone followed by doxorubicin + cyclophosphamide) in participants with early stage TNBC.

Protection of trial subjects

Subject and/or legal guardian read and understood the information provided about the study and gave written permission.

Background therapy

Evidence for comparator

Actual start date of recruitment

02 Apr 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 19

Country: Number of subjects enrolled

Belgium: 25

Country: Number of subjects enrolled

Canada: 10

Country: Number of subjects enrolled

Czechia: 20

Country: Number of subjects enrolled

France: 36

Country: Number of subjects enrolled

Germany: 55

Country: Number of subjects enrolled

Hungary: 20

Country: Number of subjects enrolled

Italy: 13

Country: Number of subjects enrolled

Korea, Republic of: 73

Country: Number of subjects enrolled

Netherlands: 3

Country: Number of subjects enrolled

Russian Federation: 23

Country: Number of subjects enrolled

Spain: 39

Country: Number of subjects enrolled

Taiwan: 8

Country: Number of subjects enrolled

United Kingdom: 8

Country: Number of subjects enrolled

United States: 282

Worldwide total number of subjects

634

EEA total number of subjects

211

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

555

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Screening procedures and baseline tumor assessments were performed within 28 days prior to the first dose of study drug (except the baseline mammogram, which could be up to 56 days prior to the start of study treatment).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Data analyst, Carer

Blinding implementation details

AbbVie, the Investigator, the study site personnel, and subject remained blinded to each subject's treatment with veliparib/placebo. AbbVie, the Investigator, the study site personnel other than pharmacy personnel, and the subject remained blinded to each subject's treatment with carboplatin/placebo throughout the course of the study.

Are arms mutually exclusive

Yes

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC

Arm description

veliparib (50 mg oral [PO] twice daily [BID]) + carboplatin (area under the curve [AUC] 6 mg/mL/min) + paclitaxel (80 mg/m^2) followed by doxorubicin/cyclophosphamide (AC)

Arm type

Experimental

Investigational medicinal product name

Veliparib

Investigational medicinal product code

ABT-888

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

50 mg veliparib for 12 weeks (or up to a maximum of 16 weeks) during Chemotherapy Segment 1

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

carboplatin (AUC 6 mg/mL/min) on Day 1 of four 21-day cycles via infusion during Chemotherapy Segment 1

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

paclitaxel (80 mg/m^2) on Day 1 of 12 weekly cycles via infusion during Chemotherapy Segment 1

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

doxorubicin (60 mg/m^2) on Day 1 of four 14-day cycles or four 21-day cycles beginning with Chemotherapy Segment 2

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

cyclophosphamide (600 mg/m^2) on Day 1 of four 14-day cycles or four 21-day cycles beginning with Chemotherapy Segment 2

Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Arm description

placebo + carboplatin (AUC 6 mg/mL/min) + paclitaxel (80 mg/m^2) followed by AC

Arm type

Placebo

Investigational medicinal product name

placebo for veliparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

placebo for veliparib for 12 weeks (or up to a maximum of 16 weeks) during Chemotherapy Segment 1

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

carboplatin (AUC 6 mg/mL/min) on Day 1 of four 21-day cycles via infusion during Chemotherapy Segment 1

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

paclitaxel (80 mg/m^2) on Day 1 of 12 weekly cycles via infusion during Chemotherapy Segment 1

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

doxorubicin (60 mg/m^2) on Day 1 of four 14-day cycles or four 21-day cycles beginning with Chemotherapy Segment 2

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

cyclophosphamide (600 mg/m^2) on Day 1 of four 14-day cycles or four 21-day cycles beginning with Chemotherapy Segment 2

Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Arm description

placebo + placebo + paclitaxel (80 mg/m^2) followed by AC

Arm type

Placebo

Investigational medicinal product name

placebo for veliparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

placebo for veliparib for 12 weeks (or up to a maximum of 16 weeks) during Chemotherapy Segment 1

Investigational medicinal product name

placebo for carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

placebo for carboplatin via infusion during Chemotherapy Segment 1

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

paclitaxel (80 mg/m^2) on Day 1 of 12 weekly cycles via infusion during Chemotherapy Segment 1

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

doxorubicin (60 mg/m^2) on Day 1 of four 14-day cycles or four 21-day cycles beginning with Chemotherapy Segment 2

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

cyclophosphamide (600 mg/m^2) on Day 1 of four 14-day cycles or four 21-day cycles beginning with Chemotherapy Segment 2

Number of subjects in period 1	Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC	Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC	Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo
Started	316	160	158
Completed	248	123	115
Not completed	68	37	43
Consent withdrawn by subject	13	8	10
Death	38	16	24
Lost to follow-up	16	10	8
Other, Not Specified	1	3	1

Baseline characteristics

Top of page

Reporting group title

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC

Reporting group description

veliparib (50 mg oral [PO] twice daily [BID]) + carboplatin (area under the curve [AUC] 6 mg/mL/min) + paclitaxel (80 mg/m^2) followed by doxorubicin/cyclophosphamide (AC)

Reporting group title

Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Reporting group description

placebo + carboplatin (AUC 6 mg/mL/min) + paclitaxel (80 mg/m^2) followed by AC

Reporting group title

Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Reporting group description

placebo + placebo + paclitaxel (80 mg/m^2) followed by AC

Reporting group values	Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC	Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC	Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo	Total
Number of subjects	316	160	158	634
Age categorical
Units: Subjects
<= 50 years	151	87	81	319
> 50 years	165	73	77	315
Gender categorical
Units: Subjects
Female	316	160	158	634
Male	0	0	0	0
Ethnicity
Units: Subjects
Hispanic or Latino	48	19	21	88
Not Hispanic or Latino	268	140	136	544
Unknown or Not Reported	0	1	1	2
Race
Units: Subjects
Asian	51	23	18	92
Native Hawaiian or Other Pacific Islander	0	2	0	2
Black or African American	33	7	15	55
White	232	127	124	483
More than one race	0	0	1	1
Unknown or Not Reported	0	1	0	1

End points

Top of page

Reporting group title

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC

Reporting group description

veliparib (50 mg oral [PO] twice daily [BID]) + carboplatin (area under the curve [AUC] 6 mg/mL/min) + paclitaxel (80 mg/m^2) followed by doxorubicin/cyclophosphamide (AC)

Reporting group title

Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Reporting group description

placebo + carboplatin (AUC 6 mg/mL/min) + paclitaxel (80 mg/m^2) followed by AC

Reporting group title

Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Reporting group description

placebo + placebo + paclitaxel (80 mg/m^2) followed by AC

Primary: Percentage of Participants With Pathological Complete Response (pCR)

Top of page

End point title

Percentage of Participants With Pathological Complete Response (pCR)

End point description

pCR in the breast tissue and the lymph node tissue was assessed upon completion of pre-operative systemic therapy and definitive surgery. pCR was defined by the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and any resected lymph node tissue following completion of neoadjuvant systemic therapy.

End point type

Primary

End point timeframe

At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug)

End point values	Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC	Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC	Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo
Number of subjects analysed	316	160	158
Units: percentage of participants
number (confidence interval 95%)	53.2 (47.7 to 58.7)	57.5 (49.8 to 65.2)	31.0 (23.8 to 38.2)

Statistical Analysis 1

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.2

Statistical Analysis 2

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference

Point estimate

-4.34

Confidence interval

level

95%

sides

2-sided

lower limit

-13.8

upper limit

5.1

Statistical Analysis 3

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density. OR was by Mantel-Haenszel method; confidence intervals were based on the normal approximation.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.357

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

1.2

Statistical Analysis 4

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density. Difference was by Mantel-Haenszel method; confidence intervals were based on the normal approximation.

Comparison groups

Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC v Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference

Point estimate

-4.43

Confidence interval

level

95%

sides

2-sided

lower limit

-13.8

upper limit

4.9

Statistical Analysis 5

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.53

Confidence interval

level

95%

sides

2-sided

lower limit

1.7

upper limit

3.8

Statistical Analysis 6

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference

Point estimate

22.15

Confidence interval

level

95%

sides

2-sided

lower limit

13.1

upper limit

31.2

Statistical Analysis 7

Statistical analysis description

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

2.57

Confidence interval

level

95%

sides

2-sided

lower limit

1.7

upper limit

3.9

Statistical Analysis 8

Statistical analysis description

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference

Point estimate

22.22

Confidence interval

level

95%

sides

2-sided

lower limit

13.2

upper limit

31.2

Secondary: Percentage of Participants With Events of Disease Progression or Death

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End point title

Percentage of Participants With Events of Disease Progression or Death

End point description

Event free survival (EFS) was secondary endpoint, defined as the time from random assignment to documentation of the first of the following events: discontinuation of study therapy due to protocol-defined progression prior to surgery; local, regional, or distant invasive recurrence of breast cancer following curative surgery; a new breast cancer; a new onset malignancy; or death as a result of any cause. Due to low event rates, the median EFS could not be estimated for any of the treatment arms. Therefore, the data table presents the percentage of participants with any of the above events within the given time frame. If a participant had not experienced any of the above events, that participant was censored at date of last available disease assessment.

End point type

Secondary

End point timeframe

Up to 4 years from the date of definitive surgery (i.e., approximately 24-36 weeks from first dose of study drug)

End point values	Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC	Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC	Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo
Number of subjects analysed	316	160	158
Units: percentage of participants
number (not applicable)	20.6	18.8	29.7

Statistical Analysis 1

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.69

Method

Logrank

Confidence interval

Statistical Analysis 2

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.778

Method

Wilcoxon p-value

Confidence interval

Statistical Analysis 3

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.69

Method

Cox proportional hazard model

Parameter type

Hazard ratio (HR)

Point estimate

1.092

Confidence interval

level

95%

sides

2-sided

lower limit

0.709

upper limit

1.683

Statistical Analysis 4

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.62

Method

Logrank

Confidence interval

Statistical Analysis 5

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.627

Method

Wilcoxon p-value

Confidence interval

Statistical Analysis 6

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.62

Method

Cox proportional hazard model

Parameter type

Hazard ratio (HR)

Point estimate

1.116

Confidence interval

level

95%

sides

2-sided

lower limit

0.724

upper limit

1.721

Statistical Analysis 8

Statistical analysis description

Unstratified analysis

Comparison groups

Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo v Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.013

Method

Wilcoxon p-value

Confidence interval

Statistical Analysis 9

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.021

Method

Cox proportional hazard model

Parameter type

Hazard ratio (HR)

Point estimate

0.643

Confidence interval

level

95%

sides

2-sided

lower limit

0.442

upper limit

0.935

Statistical Analysis 10

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015

Method

Logrank

Confidence interval

Statistical Analysis 11

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.04

Method

Wilcoxon p-value

Confidence interval

Statistical Analysis 12

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016

Method

Cox proportional hazard model

Parameter type

Hazard ratio (HR)

Point estimate

0.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.432

upper limit

0.917

Statistical Analysis 7

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.02

Method

Logrank

Confidence interval

Secondary: Percentage of Participants With an Event of Death

Top of page

End point title

Percentage of Participants With an Event of Death

End point description

Overall survival (OS) was secondary endpoint, defined as the number of days from the day the participant was randomized to the date of the participant's death. All events of death were included, regardless of whether the event occurred while the participant was still taking study drug, or after the participant discontinued study drug. Due to low event rates, the median EFS could not be estimated for any of the treatment arms. Therefore, the data table presents the percentage of participants with any of the above events within the given time frame. If a participant had not died, then the data was censored at the date when the participant was last known to be alive.

End point type

Secondary

End point timeframe

Up to 4 years from the date of definitive surgery (i.e., approximately 24-36 weeks from first dose of study drug)

End point values	Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC	Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC	Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo
Number of subjects analysed	316	160	158
Units: percentage of participants
number (not applicable)	12.0	10.0	13.9

Statistical Analysis 1

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.536

Method

Logrank

Confidence interval

Statistical Analysis 2

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.642

Method

Wilcoxon p-value

Confidence interval

Statistical Analysis 3

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.536

Method

Cox proportional hazard model

Parameter type

Hazard ratio (HR)

Point estimate

1.202

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

2.156

Statistical Analysis 4

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.454

Method

Logrank

Confidence interval

Statistical Analysis 5

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.404

Method

Wilcoxon p-value

Confidence interval

Statistical Analysis 6

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

476

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.455

Method

Cox proportional hazard model

Parameter type

Hazard ratio (HR)

Point estimate

1.25

Confidence interval

level

95%

sides

2-sided

lower limit

0.696

upper limit

2.242

Statistical Analysis 7

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.431

Method

Logrank

Confidence interval

Statistical Analysis 8

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.426

Method

Wilcoxon p-value

Confidence interval

Statistical Analysis 9

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.432

Method

Cox proportional hazard model

Parameter type

Hazard ratio (HR)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.479

upper limit

1.37

Statistical Analysis 10

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.454

Method

Logrank

Confidence interval

Statistical Analysis 11

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.837

Method

Wilcoxon p-value

Confidence interval

Statistical Analysis 12

Statistical analysis description

Stratified analysis: all calculations were stratified by breast cancer gene (BRCA) status, lymph node stage, and dose density.

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

474

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.452

Method

Cox proportional hazard model

Parameter type

Hazard ratio (HR)

Point estimate

0.817

Confidence interval

level

95%

sides

2-sided

lower limit

0.483

upper limit

1.383

Secondary: Percentage of Participants Eligible for Breast Conservation After Therapy

Top of page

End point title

Percentage of Participants Eligible for Breast Conservation After Therapy

End point description

Whether a participant was eligible for breast conserving surgery for whom mastectomy was planned at diagnosis was determined by the participant's surgeon prior to chemotherapy and after completion of chemotherapy. The breast conservation rate (BCR) was defined as the rate at which participants are eligible for breast conservation after neoadjuvant therapy among participants for whom mastectomy was planned at diagnosis, and is presented as the percentage of participants eligible for breast conservation after therapy among participants who were deemed ineligible for breast conservation surgery at screening. Randomized participants who were deemed ineligible for breast conservation surgery at screening. Only participants with evaluations at both screening and pre-op visits were included.

End point type

Secondary

End point timeframe

At the time of definitive surgery (approximately 24-36 weeks from first dose of study drug)

End point values	Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC	Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC	Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo
Number of subjects analysed	73	34	34
Units: percentage of particiants
number (confidence interval 95%)	61.6 (50.5 to 72.8)	44.1 (27.4 to 60.8)	44.1 (27.4 to 60.8)

Statistical Analysis 1

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

4.6

Statistical Analysis 2

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference

Point estimate

17.53

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

37.6

Statistical Analysis 3

Statistical analysis description

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

4.5

Statistical Analysis 4

Statistical analysis description

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.132

Method

Cochran-Mantel-Haenszel

Parameter type

Difference

Point estimate

15.82

Confidence interval

level

95%

sides

2-sided

lower limit

-4.3

upper limit

35.9

Statistical Analysis 5

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

2.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

4.6

Statistical Analysis 6

Statistical analysis description

Unstratified analysis

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference

Point estimate

17.53

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

37.6

Statistical Analysis 7

Statistical analysis description

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Odds ratio (OR)

Point estimate

1.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

4.5

Statistical Analysis 8

Statistical analysis description

Comparison groups

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC v Arm C: Placebo + Placebo + Paclitaxel, Followed by AC placebo

Number of subjects included in analysis

107

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.139

Method

Cochran-Mantel-Haenszel

Parameter type

Difference

Point estimate

15.85

Confidence interval

level

95%

sides

2-sided

lower limit

-4.6

upper limit

36.3

Adverse events

Top of page

Timeframe for reporting adverse events

From first dose of study drug through 30 days following discontinuation of study drug administration; up to a maximum of 150 days.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC

Reporting group description

veliparib (50 mg PO BID) + carboplatin (AUC 6 mg/mL/min) + paclitaxel (80 mg/m^2) followed by AC

Reporting group title

Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC

Reporting group description

placebo + carboplatin (AUC 6 mg/mL/min) + paclitaxel (80 mg/m^2) followed by AC

Reporting group title

Arm C: Placebo + Placebo + Paclitaxel, Followed by AC

Reporting group description

placebo + placebo + paclitaxel (80 mg/m^2) followed by AC

Serious adverse events	Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC	Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC	Arm C: Placebo + Placebo + Paclitaxel, Followed by AC
Total subjects affected by serious adverse events
subjects affected / exposed	95 / 313 (30.35%)	22 / 157 (14.01%)	42 / 158 (26.58%)
number of deaths (all causes)	38	22	16
number of deaths resulting from adverse events	1	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO MENINGES
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
DEEP VEIN THROMBOSIS
subjects affected / exposed	1 / 313 (0.32%)	1 / 157 (0.64%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 1	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
EMBOLISM
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPERTENSION
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
DEATH
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
FATIGUE
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MALAISE
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NON-CARDIAC CHEST PAIN
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PYREXIA
subjects affected / exposed	4 / 313 (1.28%)	1 / 157 (0.64%)	2 / 158 (1.27%)
occurrences causally related to treatment / all	1 / 5	0 / 1	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
subjects affected / exposed	2 / 313 (0.64%)	2 / 157 (1.27%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPOXIA
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PAINFUL RESPIRATION
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONITIS
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PULMONARY EMBOLISM
subjects affected / exposed	6 / 313 (1.92%)	3 / 157 (1.91%)	2 / 158 (1.27%)
occurrences causally related to treatment / all	2 / 6	2 / 3	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
ADJUSTMENT DISORDER WITH DEPRESSED MOOD
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ANXIETY
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MENTAL STATUS CHANGES
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PSYCHOGENIC SEIZURE
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
ELECTROCARDIOGRAM QT PROLONGED
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
ANKLE FRACTURE
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FEMORAL NECK FRACTURE
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INFUSION RELATED REACTION
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RIB FRACTURE
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
WOUND SECRETION
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
WRIST FRACTURE
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
ATRIAL FIBRILLATION
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ATRIAL FLUTTER
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MYOCARDIAL ISCHAEMIA
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SINUS TACHYCARDIA
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SUPRAVENTRICULAR EXTRASYSTOLES
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SUPRAVENTRICULAR TACHYCARDIA
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TACHYCARDIA
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VENTRICULAR EXTRASYSTOLES
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
CEREBROVASCULAR ACCIDENT
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DIZZINESS
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HEADACHE
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MIGRAINE WITH AURA
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PARTIAL SEIZURES
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SEIZURE
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SYNCOPE
subjects affected / exposed	3 / 313 (0.96%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	11 / 313 (3.51%)	3 / 157 (1.91%)	6 / 158 (3.80%)
occurrences causally related to treatment / all	3 / 14	0 / 3	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FEBRILE NEUTROPENIA
subjects affected / exposed	51 / 313 (16.29%)	6 / 157 (3.82%)	23 / 158 (14.56%)
occurrences causally related to treatment / all	5 / 55	0 / 6	1 / 26
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LEUKOPENIA
subjects affected / exposed	0 / 313 (0.00%)	2 / 157 (1.27%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NEUTROPENIA
subjects affected / exposed	4 / 313 (1.28%)	1 / 157 (0.64%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PANCYTOPENIA
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
THROMBOCYTOPENIA
subjects affected / exposed	4 / 313 (1.28%)	0 / 157 (0.00%)	2 / 158 (1.27%)
occurrences causally related to treatment / all	1 / 4	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
ABDOMINAL PAIN
subjects affected / exposed	2 / 313 (0.64%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ABDOMINAL PAIN UPPER
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DIARRHOEA
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ENTEROCOLITIS
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HAEMORRHOIDAL HAEMORRHAGE
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MALLORY-WEISS SYNDROME
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NAUSEA
subjects affected / exposed	6 / 313 (1.92%)	2 / 157 (1.27%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NEUTROPENIC COLITIS
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PROCTALGIA
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RECTAL HAEMORRHAGE
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	3 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
STOMATITIS
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VOMITING
subjects affected / exposed	3 / 313 (0.96%)	2 / 157 (1.27%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	1 / 5	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
HEPATITIS
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
HIDRADENITIS
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
ACUTE KIDNEY INJURY
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MUSCULAR WEAKNESS
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
ATYPICAL PNEUMONIA
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BACTERAEMIA
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	2 / 158 (1.27%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BRONCHITIS
subjects affected / exposed	2 / 313 (0.64%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CELLULITIS
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CLOSTRIDIUM DIFFICILE COLITIS
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CLOSTRIDIUM DIFFICILE INFECTION
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CYSTITIS
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DEVICE RELATED SEPSIS
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ENTEROCOLITIS INFECTIOUS
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	2 / 158 (1.27%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ENTEROCOLITIS VIRAL
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HERPES SIMPLEX MENINGITIS
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INFLUENZA
subjects affected / exposed	1 / 313 (0.32%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
OESOPHAGEAL CANDIDIASIS
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMOCYSTIS JIROVECII PNEUMONIA
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	4 / 313 (1.28%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PYELONEPHRITIS
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SEPSIS
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SINUSITIS
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TONSILLITIS
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TOOTH ABSCESS
subjects affected / exposed	2 / 313 (0.64%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URINARY TRACT INFECTION
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	3 / 158 (1.90%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VASCULAR DEVICE INFECTION
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VIRAL INFECTION
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VULVAL ABSCESS
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
WOUND INFECTION
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
DEHYDRATION
subjects affected / exposed	0 / 313 (0.00%)	1 / 157 (0.64%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPOKALAEMIA
subjects affected / exposed	0 / 313 (0.00%)	0 / 157 (0.00%)	1 / 158 (0.63%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPONATRAEMIA
subjects affected / exposed	1 / 313 (0.32%)	0 / 157 (0.00%)	0 / 158 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Arm A: Veliparib + Carboplatin + Paclitaxel, Followed by AC	Arm B: Placebo + Carboplatin + Paclitaxel, Followed by AC	Arm C: Placebo + Placebo + Paclitaxel, Followed by AC
Total subjects affected by non serious adverse events
subjects affected / exposed	312 / 313 (99.68%)	157 / 157 (100.00%)	158 / 158 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN
subjects affected / exposed	3 / 313 (0.96%)	8 / 157 (5.10%)	0 / 158 (0.00%)
occurrences all number	3	8	0
Vascular disorders
FLUSHING
subjects affected / exposed	11 / 313 (3.51%)	9 / 157 (5.73%)	7 / 158 (4.43%)
occurrences all number	14	10	7
HOT FLUSH
subjects affected / exposed	51 / 313 (16.29%)	22 / 157 (14.01%)	28 / 158 (17.72%)
occurrences all number	63	27	34
HYPERTENSION
subjects affected / exposed	17 / 313 (5.43%)	6 / 157 (3.82%)	3 / 158 (1.90%)
occurrences all number	27	7	3
General disorders and administration site conditions
ASTHENIA
subjects affected / exposed	51 / 313 (16.29%)	20 / 157 (12.74%)	25 / 158 (15.82%)
occurrences all number	134	43	64
FATIGUE
subjects affected / exposed	183 / 313 (58.47%)	89 / 157 (56.69%)	92 / 158 (58.23%)
occurrences all number	339	158	169
INFLUENZA LIKE ILLNESS
subjects affected / exposed	17 / 313 (5.43%)	4 / 157 (2.55%)	2 / 158 (1.27%)
occurrences all number	18	8	2
OEDEMA PERIPHERAL
subjects affected / exposed	29 / 313 (9.27%)	16 / 157 (10.19%)	15 / 158 (9.49%)
occurrences all number	32	19	18
PAIN
subjects affected / exposed	17 / 313 (5.43%)	8 / 157 (5.10%)	9 / 158 (5.70%)
occurrences all number	22	9	10
PYREXIA
subjects affected / exposed	39 / 313 (12.46%)	16 / 157 (10.19%)	15 / 158 (9.49%)
occurrences all number	49	22	17
Immune system disorders
DRUG HYPERSENSITIVITY
subjects affected / exposed	12 / 313 (3.83%)	2 / 157 (1.27%)	9 / 158 (5.70%)
occurrences all number	14	2	10
Reproductive system and breast disorders
BREAST PAIN
subjects affected / exposed	7 / 313 (2.24%)	13 / 157 (8.28%)	3 / 158 (1.90%)
occurrences all number	7	14	6
Respiratory, thoracic and mediastinal disorders
COUGH
subjects affected / exposed	64 / 313 (20.45%)	24 / 157 (15.29%)	25 / 158 (15.82%)
occurrences all number	77	31	30
DYSPNOEA
subjects affected / exposed	55 / 313 (17.57%)	21 / 157 (13.38%)	31 / 158 (19.62%)
occurrences all number	73	26	44
EPISTAXIS
subjects affected / exposed	46 / 313 (14.70%)	27 / 157 (17.20%)	21 / 158 (13.29%)
occurrences all number	52	31	22
NASAL CONGESTION
subjects affected / exposed	13 / 313 (4.15%)	11 / 157 (7.01%)	6 / 158 (3.80%)
occurrences all number	15	13	6
OROPHARYNGEAL PAIN
subjects affected / exposed	26 / 313 (8.31%)	8 / 157 (5.10%)	16 / 158 (10.13%)
occurrences all number	28	9	16
Psychiatric disorders
ANXIETY
subjects affected / exposed	24 / 313 (7.67%)	18 / 157 (11.46%)	15 / 158 (9.49%)
occurrences all number	27	18	17
INSOMNIA
subjects affected / exposed	71 / 313 (22.68%)	31 / 157 (19.75%)	37 / 158 (23.42%)
occurrences all number	75	36	43
Investigations
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	32 / 313 (10.22%)	10 / 157 (6.37%)	18 / 158 (11.39%)
occurrences all number	51	15	27
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	26 / 313 (8.31%)	6 / 157 (3.82%)	16 / 158 (10.13%)
occurrences all number	40	6	24
WEIGHT DECREASED
subjects affected / exposed	9 / 313 (2.88%)	3 / 157 (1.91%)	8 / 158 (5.06%)
occurrences all number	11	4	10
Nervous system disorders
DIZZINESS
subjects affected / exposed	55 / 313 (17.57%)	20 / 157 (12.74%)	24 / 158 (15.19%)
occurrences all number	64	22	34
DYSGEUSIA
subjects affected / exposed	75 / 313 (23.96%)	29 / 157 (18.47%)	39 / 158 (24.68%)
occurrences all number	82	32	40
HEADACHE
subjects affected / exposed	88 / 313 (28.12%)	46 / 157 (29.30%)	40 / 158 (25.32%)
occurrences all number	109	63	53
PARAESTHESIA
subjects affected / exposed	31 / 313 (9.90%)	12 / 157 (7.64%)	17 / 158 (10.76%)
occurrences all number	41	21	19
PERIPHERAL SENSORY NEUROPATHY
subjects affected / exposed	135 / 313 (43.13%)	77 / 157 (49.04%)	70 / 158 (44.30%)
occurrences all number	190	121	93
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	212 / 313 (67.73%)	37 / 157 (23.57%)	105 / 158 (66.46%)
occurrences all number	632	59	281
LEUKOPENIA
subjects affected / exposed	62 / 313 (19.81%)	21 / 157 (13.38%)	43 / 158 (27.22%)
occurrences all number	138	33	102
NEUTROPENIA
subjects affected / exposed	237 / 313 (75.72%)	45 / 157 (28.66%)	115 / 158 (72.78%)
occurrences all number	836	96	406
THROMBOCYTOPENIA
subjects affected / exposed	169 / 313 (53.99%)	4 / 157 (2.55%)	67 / 158 (42.41%)
occurrences all number	460	6	147
Eye disorders
DRY EYE
subjects affected / exposed	14 / 313 (4.47%)	9 / 157 (5.73%)	5 / 158 (3.16%)
occurrences all number	14	10	5
VISION BLURRED
subjects affected / exposed	11 / 313 (3.51%)	8 / 157 (5.10%)	4 / 158 (2.53%)
occurrences all number	11	9	4
Gastrointestinal disorders
ABDOMINAL PAIN
subjects affected / exposed	37 / 313 (11.82%)	13 / 157 (8.28%)	21 / 158 (13.29%)
occurrences all number	45	19	27
ABDOMINAL PAIN UPPER
subjects affected / exposed	25 / 313 (7.99%)	9 / 157 (5.73%)	6 / 158 (3.80%)
occurrences all number	37	11	9
CONSTIPATION
subjects affected / exposed	135 / 313 (43.13%)	71 / 157 (45.22%)	62 / 158 (39.24%)
occurrences all number	168	102	77
DIARRHOEA
subjects affected / exposed	120 / 313 (38.34%)	58 / 157 (36.94%)	50 / 158 (31.65%)
occurrences all number	184	78	68
DRY MOUTH
subjects affected / exposed	24 / 313 (7.67%)	9 / 157 (5.73%)	3 / 158 (1.90%)
occurrences all number	26	9	3
DYSPEPSIA
subjects affected / exposed	46 / 313 (14.70%)	29 / 157 (18.47%)	32 / 158 (20.25%)
occurrences all number	60	43	38
GASTROOESOPHAGEAL REFLUX DISEASE
subjects affected / exposed	30 / 313 (9.58%)	13 / 157 (8.28%)	9 / 158 (5.70%)
occurrences all number	36	18	9
NAUSEA
subjects affected / exposed	225 / 313 (71.88%)	98 / 157 (62.42%)	119 / 158 (75.32%)
occurrences all number	450	169	256
STOMATITIS
subjects affected / exposed	121 / 313 (38.66%)	41 / 157 (26.11%)	48 / 158 (30.38%)
occurrences all number	162	49	67
VOMITING
subjects affected / exposed	90 / 313 (28.75%)	26 / 157 (16.56%)	58 / 158 (36.71%)
occurrences all number	130	38	93
Skin and subcutaneous tissue disorders
ALOPECIA
subjects affected / exposed	190 / 313 (60.70%)	102 / 157 (64.97%)	95 / 158 (60.13%)
occurrences all number	231	120	119
DERMATITIS ACNEIFORM
subjects affected / exposed	25 / 313 (7.99%)	16 / 157 (10.19%)	10 / 158 (6.33%)
occurrences all number	29	18	13
DRY SKIN
subjects affected / exposed	9 / 313 (2.88%)	8 / 157 (5.10%)	5 / 158 (3.16%)
occurrences all number	9	8	5
ERYTHEMA
subjects affected / exposed	4 / 313 (1.28%)	10 / 157 (6.37%)	4 / 158 (2.53%)
occurrences all number	5	10	5
NAIL DISCOLOURATION
subjects affected / exposed	20 / 313 (6.39%)	10 / 157 (6.37%)	7 / 158 (4.43%)
occurrences all number	20	10	7
NAIL DISORDER
subjects affected / exposed	12 / 313 (3.83%)	9 / 157 (5.73%)	7 / 158 (4.43%)
occurrences all number	12	10	7
ONYCHOLYSIS
subjects affected / exposed	2 / 313 (0.64%)	8 / 157 (5.10%)	7 / 158 (4.43%)
occurrences all number	2	9	8
PRURITUS
subjects affected / exposed	21 / 313 (6.71%)	12 / 157 (7.64%)	14 / 158 (8.86%)
occurrences all number	25	15	14
RASH
subjects affected / exposed	25 / 313 (7.99%)	9 / 157 (5.73%)	13 / 158 (8.23%)
occurrences all number	26	10	16
RASH MACULO-PAPULAR
subjects affected / exposed	17 / 313 (5.43%)	8 / 157 (5.10%)	4 / 158 (2.53%)
occurrences all number	27	13	5
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	37 / 313 (11.82%)	37 / 157 (23.57%)	25 / 158 (15.82%)
occurrences all number	52	41	35
BACK PAIN
subjects affected / exposed	34 / 313 (10.86%)	13 / 157 (8.28%)	14 / 158 (8.86%)
occurrences all number	40	13	14
BONE PAIN
subjects affected / exposed	43 / 313 (13.74%)	11 / 157 (7.01%)	18 / 158 (11.39%)
occurrences all number	49	12	23
MUSCLE SPASMS
subjects affected / exposed	16 / 313 (5.11%)	3 / 157 (1.91%)	6 / 158 (3.80%)
occurrences all number	19	3	6
MUSCULAR WEAKNESS
subjects affected / exposed	16 / 313 (5.11%)	4 / 157 (2.55%)	3 / 158 (1.90%)
occurrences all number	18	4	4
MYALGIA
subjects affected / exposed	67 / 313 (21.41%)	37 / 157 (23.57%)	31 / 158 (19.62%)
occurrences all number	96	48	45
PAIN IN EXTREMITY
subjects affected / exposed	20 / 313 (6.39%)	8 / 157 (5.10%)	15 / 158 (9.49%)
occurrences all number	23	8	18
Infections and infestations
FOLLICULITIS
subjects affected / exposed	7 / 313 (2.24%)	10 / 157 (6.37%)	7 / 158 (4.43%)
occurrences all number	9	12	7
NASOPHARYNGITIS
subjects affected / exposed	23 / 313 (7.35%)	10 / 157 (6.37%)	10 / 158 (6.33%)
occurrences all number	28	12	12
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	27 / 313 (8.63%)	13 / 157 (8.28%)	10 / 158 (6.33%)
occurrences all number	35	14	13
URINARY TRACT INFECTION
subjects affected / exposed	22 / 313 (7.03%)	12 / 157 (7.64%)	12 / 158 (7.59%)
occurrences all number	27	14	14
Metabolism and nutrition disorders
DECREASED APPETITE
subjects affected / exposed	74 / 313 (23.64%)	28 / 157 (17.83%)	39 / 158 (24.68%)
occurrences all number	96	44	57
DEHYDRATION
subjects affected / exposed	25 / 313 (7.99%)	8 / 157 (5.10%)	15 / 158 (9.49%)
occurrences all number	52	19	27
HYPERGLYCAEMIA
subjects affected / exposed	12 / 313 (3.83%)	5 / 157 (3.18%)	10 / 158 (6.33%)
occurrences all number	16	8	16
HYPOKALAEMIA
subjects affected / exposed	36 / 313 (11.50%)	11 / 157 (7.01%)	16 / 158 (10.13%)
occurrences all number	56	14	29
HYPOMAGNESAEMIA
subjects affected / exposed	23 / 313 (7.35%)	2 / 157 (1.27%)	10 / 158 (6.33%)
occurrences all number	34	2	12

More information

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Were there any global substantial amendments to the protocol? Yes

24 Nov 2013

• Update Residual Cancer Burden (RCB) to a tertiary endpoint and clarify that RCB information will not be collected from all sites. • Revise pregnancy testing requirements; Remove 3 hour PK sample at paclitaxel (P)1 visit and request PK samples at P1 visit only if feasible. • Updated the blood samples for Pharmacogenetic analysis to include the collection of an additional (optional) 4mL whole blood sample (for a total of 2 samples) at P1. • Clarify plan for tumor biopsy collection and remove biopsy collection at AC1; Add Quality of Life Questionnaire (QLQ)-C30 questionnaire in the study procedures, remove Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (QLQ CIPN20) questionnaire and revise the frequency and duration of collection. • Update survival data collection frequency to every 6 months and clarify which data points will be collected in the survival portion of the study.

01 Apr 2014

• Update Inclusion Criterion 7 to require the use of contraception for 6 months following completion of therapy. • Add Inclusion Criterion 9 to ensure subjects are capable of taking oral medication. • Add requirement for pregnancy testing at P4, P7, P10 and AC1 visits. • Add requirement for urine testing at AC2 and AC4 visits.

22 Jul 2014

• Increase approximate number of participating sites to 250. • Update clinical stage in Inclusion Criterion 2 to T2-3 N0-2 or T1 N1-2. • Allow for subjects with Stage III disease to undergo alternate imaging per local standards.

25 Nov 2014

• Update Study Procedures, Medical History and Oncology History to collect menses history and family history of breast and ovarian cancer to evaluate (post-study analysis) for chemotherapy induced amenorrhea and to generate hypotheses around benefits of investigational therapy in subjects with or without a family history of breast and/or ovarian cancer. • Update PK methods to include additional timepoints to collect a sample for analysis to coincide with the time of relapse; increase the sample volume for plasma markers to ensure sufficient plasma is available for testing using the current methods; include circulating nucleic acid sample collection for additional sequencing studies. • Correct the duration for avoiding pregnancy from 90 days to 6 months to align with Inclusion Criterion.

31 Aug 2016

• Update appropriate sections to move Event Free Survival (EFS) and Overall Survival (OS) from Tertiary Efficacy Endpoints to Secondary Efficacy Endpoints • Change primary contact for protocol deviations.

25 Oct 2018

• Revise the duration subjects will be evaluated for disease recurrent during the Post-Surgery Follow-Up period for the secondary endpoint of event-free survival (EFS). • Update primary study contacts for protocol deviations.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Primary: Percentage of Participants With Pathological Complete Response (pCR)

Primary: Percentage of Participants With Pathological Complete Response (pCR)

Secondary: Percentage of Participants With Events of Disease Progression or Death

Secondary: Percentage of Participants With Events of Disease Progression or Death

Secondary: Percentage of Participants With an Event of Death

Secondary: Percentage of Participants With an Event of Death

Secondary: Percentage of Participants Eligible for Breast Conservation After Therapy

Secondary: Percentage of Participants Eligible for Breast Conservation After Therapy

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA