Trial Outcomes & Findings for A Randomized Trial of Ixempra Versus Taxol in Adjuvant Therapy of Triple Negative Breast Cancer (NCT NCT00789581)

Last Updated: 2017-07-02

Results Overview

The percentage of participants with disease-free survival at 3 and 5 years. Disease-free survival (DFS) is measured from the time between randomization and the date of first documented disease recurrence, or death from any cause.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

614 participants

Primary outcome timeframe

up to 5.25 years (63 months)

Results posted on

2017-07-02

Participant Flow

The trial was designed to evaluate if doxorubicin+cyclophosphamide (AC) followed by ixabepilone was more effective than AC followed by standard weekly paclitaxel as adjuvant treatment for patients with operable triple negative breast cancer (TNBC). Between Dec 2008 and Jan 2011, 614 women with early-stage TNBC were enrolled from 63 U.S. sites.

Subjects were randomized in a 1:1 ratio to either of 2 arms: 306 to AC/Ixabepilone (Ixa); 308 to AC/paclitaxel (Pac). 489 patients completed all planned treatment with AC/Ixa or AC/Pac.

Participant milestones

Participant milestones
Measure	AC/Ixabepilone Doxorubicin+cyclophosphamide (AC) every 3 weeks for 4 cycles (12 weeks), followed by ixabepilone every 3 weeks for 4 cycles (12 weeks). Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Ixabepilone (Ixempra): 40 mg/m2	AC/Paclitaxel Doxorubicin+cyclophosphamide (AC) every 3 weeks for 4 cycles (12 weeks), followed by weekly paclitaxel for 12 weeks. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Paclitaxel (Taxol): 80 mg/m2
AC Therapy STARTED	306	308
AC Therapy COMPLETED	295	291
AC Therapy NOT COMPLETED	11	17
Adjuvant Therapy STARTED	295	291
Adjuvant Therapy COMPLETED	255	234
Adjuvant Therapy NOT COMPLETED	40	57

Reasons for withdrawal

Reasons for withdrawal
Measure	AC/Ixabepilone Doxorubicin+cyclophosphamide (AC) every 3 weeks for 4 cycles (12 weeks), followed by ixabepilone every 3 weeks for 4 cycles (12 weeks). Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Ixabepilone (Ixempra): 40 mg/m2	AC/Paclitaxel Doxorubicin+cyclophosphamide (AC) every 3 weeks for 4 cycles (12 weeks), followed by weekly paclitaxel for 12 weeks. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Paclitaxel (Taxol): 80 mg/m2
AC Therapy Adverse Event	2	3
AC Therapy Withdrawal by Subject	4	7
AC Therapy Disease recurrence	3	1
AC Therapy Intercurrent Illness	1	0
AC Therapy Never Treated	1	4
AC Therapy Other	0	2
Adjuvant Therapy Never treated	2	2
Adjuvant Therapy Adverse Event	20	44
Adjuvant Therapy Withdrawal by Subject	14	5
Adjuvant Therapy Disease recurrence	2	1
Adjuvant Therapy Intercurrent Illness	1	3
Adjuvant Therapy Protocol Violation	1	1
Adjuvant Therapy Other	0	1

Baseline Characteristics

A Randomized Trial of Ixempra Versus Taxol in Adjuvant Therapy of Triple Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ixabepilone n=306 Participants Doxorubicin and cyclophosphamide (AC) given every 3 weeks for 4 cycles, followed by ixabepilone every 3 weeks for 4 cycles. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Ixabepilone (Ixempra): 40 mg/m2	Paclitaxel n=308 Participants Doxorubicin and cyclophosphamide (AC) given every 3 weeks for 4 cycles, followed by paclitaxel weekly for 12 weeks. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Paclitaxel (Taxol): 80 mg/m2	Total n=614 Participants Total of all reporting groups
Age, Customized <50 years	124 Participants n=5 Participants	93 Participants n=7 Participants	217 Participants n=5 Participants
Age, Customized ≥50 years	182 Participants n=5 Participants	215 Participants n=7 Participants	397 Participants n=5 Participants
Sex: Female, Male Female	306 Participants n=5 Participants	308 Participants n=7 Participants	614 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	61 Participants n=5 Participants	52 Participants n=7 Participants	113 Participants n=5 Participants
Race (NIH/OMB) White	237 Participants n=5 Participants	251 Participants n=7 Participants	488 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Menopausal Status Premenopausal	100 Participants n=5 Participants	84 Participants n=7 Participants	184 Participants n=5 Participants
Menopausal Status Postmenopausal	206 Participants n=5 Participants	224 Participants n=7 Participants	430 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 5.25 years (63 months)

Population: The intent-to-treat population (all randomized patients) are included in the analysis.

Outcome measures

Outcome measures
Measure	Ixabepilone n=306 Participants Doxorubicin and cyclophosphamide (AC) given every 3 weeks for 4 cycles, followed by ixabepilone every 3 weeks for 4 cycles. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Ixabepilone (Ixempra): 40 mg/m2	Paclitaxel n=308 Participants Doxorubicin and cyclophosphamide (AC) given every 3 weeks for 4 cycles, followed by paclitaxel given weekly for 12 weeks. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Paclitaxel (Taxol): 80 mg/m2
Disease-free Survival 3-year DFS	88.6 percentage of participants Interval 84.3 to 91.8	88.8 percentage of participants Interval 84.6 to 91.9
Disease-free Survival 5-year DFS	87.1 percentage of participants Interval 82.6 to 90.5	84.7 percentage of participants Interval 79.7 to 88.6

SECONDARY outcome

Timeframe: up to 5.25 years (63 months)

Population: The intent-to-treat population (all randomized patients) are included in the analysis.

The percentage of participants with overall survival at 3 and 5 years are presented. Overall survival (OS) defined as the time between randomization to date of death from any cause.

Outcome measures

Outcome measures
Measure	Ixabepilone n=306 Participants Doxorubicin and cyclophosphamide (AC) given every 3 weeks for 4 cycles, followed by ixabepilone every 3 weeks for 4 cycles. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Ixabepilone (Ixempra): 40 mg/m2	Paclitaxel n=308 Participants Doxorubicin and cyclophosphamide (AC) given every 3 weeks for 4 cycles, followed by paclitaxel given weekly for 12 weeks. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Paclitaxel (Taxol): 80 mg/m2
Overall Survival 3-year OS	92.4 percentage of participants Interval 86.9 to 93.7	93.8 percentage of participants Interval 90.2 to 96.1
Overall Survival 5-year OS	89.7 percentage of participants Interval 85.5 to 92.7	89.6 percentage of participants Interval 85.0 to 92.9

Adverse Events

Ixabepilone

Serious events: 58 serious events

Other events: 305 other events

Deaths: 0 deaths

Paclitaxel

Serious events: 50 serious events

Other events: 304 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Charles H. Davis, RAC

Sarah Cannon Development Innovations

Phone: 615 524-4341

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Ixabepilone n=305 participants at risk Doxorubicin and cyclophosphamide (AC) given every 3 weeks for 4 cycles, followed by ixabepilone every 3 weeks for 4 cycles. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Ixabepilone (Ixempra): 40 mg/m2	Paclitaxel n=304 participants at risk Doxorubicin and cyclophosphamide (AC) given every 3 weeks for 4 cycles, followed by paclitaxel given weekly for 12 weeks. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Paclitaxel (Taxol): 80 mg/m2
Blood and lymphatic system disorders FEBRILE NEUTROPENIA	3.9% 12/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	3.9% 12/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	1.6% 5/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.33% 1/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Infections and infestations INFECTION	1.3% 4/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.99% 3/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders NAUSEA	0.98% 3/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.99% 3/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Blood and lymphatic system disorders NEUTROPENIA	1.3% 4/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.33% 1/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Infections and infestations SEPSIS	0.98% 3/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders VOMITING	0.98% 3/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.66% 2/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Blood and lymphatic system disorders ANAEMIA	0.66% 2/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Infections and infestations CELLULITIS	0.66% 2/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
General disorders CHEST PAIN	0.66% 2/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders DIARRHOEA	0.66% 2/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	1.6% 5/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.66% 2/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.33% 1/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Investigations NEUTROPHIL COUNT	0.66% 2/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
General disorders PAIN	0.66% 2/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Nervous system disorders SYNCOPE	0.66% 2/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.33% 1/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders ABDOMINAL PAIN	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.66% 2/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Vascular disorders AORTIC STENOSIS	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Cardiac disorders ATRIAL FIBRILLATION	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.33% 1/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Musculoskeletal and connective tissue disorders BACK PAIN	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.33% 1/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Musculoskeletal and connective tissue disorders BONE PAIN	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Reproductive system and breast disorders BREAST PAIN	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Nervous system disorders CEREBROVASCULAR ACCIDENT	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Infections and infestations CHEST WALL ABSCESS	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Infections and infestations CLOSTRIDIUM DIFFICILE COLITIS	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders COLITIS	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Vascular disorders DEEP VEIN THROMBOSIS	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.99% 3/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Psychiatric disorders DEPRESSION	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Infections and infestations DEVICE RELATED INFECTION	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Cardiac disorders DIASTOLIC DYSFUNCTION	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ENDOMETRIAL CANCER	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders EROSIVE OESOPHAGITIS	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Congenital, familial and genetic disorders FANCONI SYNDROME	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
General disorders FATIGUE	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Injury, poisoning and procedural complications FEMUR FRACTURE	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.33% 1/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Metabolism and nutrition disorders HYPONATRAEMIA	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Vascular disorders HYPOTENSION	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	1.3% 4/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Blood and lymphatic system disorders LEUKOPENIA	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Infections and infestations NEUTROPENIC INFECTION	0.33% 1/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	0.00% 0/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.

Other adverse events
Measure	Ixabepilone n=305 participants at risk Doxorubicin and cyclophosphamide (AC) given every 3 weeks for 4 cycles, followed by ixabepilone every 3 weeks for 4 cycles. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Ixabepilone (Ixempra): 40 mg/m2	Paclitaxel n=304 participants at risk Doxorubicin and cyclophosphamide (AC) given every 3 weeks for 4 cycles, followed by paclitaxel given weekly for 12 weeks. Doxorubicin: 60 mg/m2 Cyclophosphamide: 600 mg/m2 Paclitaxel (Taxol): 80 mg/m2
Gastrointestinal disorders Nausea	74.4% 227/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	72.7% 221/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders Constipation	43.0% 131/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	40.1% 122/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders Diarrhoea	36.7% 112/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	37.5% 114/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders Vomiting	29.2% 89/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	22.7% 69/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders Dyspepsia	17.4% 53/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	16.8% 51/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders Stomatitis	17.0% 52/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	16.8% 51/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders Gastroesophageal reflux	8.5% 26/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	8.6% 26/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Gastrointestinal disorders Abdominal pain	6.6% 20/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	7.2% 22/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
General disorders Fatigue	82.0% 250/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	82.6% 251/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
General disorders Mucosal Inflammation	26.6% 81/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	21.1% 64/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
General disorders Pyrexia	15.4% 47/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	16.4% 50/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
General disorders Oedema Peripheral	11.8% 36/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	19.1% 58/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
General disorders Pain	15.4% 47/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	8.9% 27/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Skin and subcutaneous tissue disorders Alopecia	70.2% 214/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	68.4% 208/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Skin and subcutaneous tissue disorders Rash	10.8% 33/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	15.5% 47/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Skin and subcutaneous tissue disorders Nail disorder	9.2% 28/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	14.8% 45/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Skin and subcutaneous tissue disorders Dry skin	6.6% 20/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	6.2% 19/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Skin and subcutaneous tissue disorders Pruritis	5.9% 18/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	5.3% 16/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Nervous system disorders Neuropathy peripheral	39.3% 120/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	52.0% 158/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Nervous system disorders Headache	28.5% 87/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	28.9% 88/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Nervous system disorders Dysgeusia	25.6% 78/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	22.7% 69/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Nervous system disorders Peripheral Sensory neuropathy	18.0% 55/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	21.4% 65/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Nervous system disorders Dizziness	12.1% 37/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	13.5% 41/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Nervous system disorders Paraesthesia	5.2% 16/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	6.2% 19/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Musculoskeletal and connective tissue disorders Arthralgia	34.8% 106/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	28.6% 87/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Musculoskeletal and connective tissue disorders Bone Pain	27.2% 83/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	15.1% 46/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Musculoskeletal and connective tissue disorders Myalgia	22.0% 67/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	17.4% 53/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Musculoskeletal and connective tissue disorders Pain in Extremity	15.4% 47/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	13.2% 40/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Musculoskeletal and connective tissue disorders Back Pain	13.4% 41/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	10.9% 33/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	12.1% 37/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	7.2% 22/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Musculoskeletal and connective tissue disorders Muscle spasms	5.2% 16/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	6.6% 20/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Blood and lymphatic system disorders Neutropenia	45.6% 139/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	47.7% 145/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Blood and lymphatic system disorders Anaemia	34.1% 104/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	39.1% 119/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Blood and lymphatic system disorders Leukopenia	22.6% 69/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	27.3% 83/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Blood and lymphatic system disorders Thrombocytopenia	14.8% 45/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	11.8% 36/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Infections and infestations Upper respiratory tract infection	11.1% 34/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	6.6% 20/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Infections and infestations Urinary tract infection	8.5% 26/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	9.2% 28/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Infections and infestations Sinusitis	6.9% 21/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	10.9% 33/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Respiratory, thoracic and mediastinal disorders Cough	18.7% 57/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	21.7% 66/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.8% 42/305 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.	16.4% 50/304 • Every 3 weeks up to 28 weeks Adverse events (AEs) were collected for all patients who received at least 1 dose of treatment - from date of first treatment through the 30-day end of treatment period. All patients had at least one AE.