Measure Type	Primary
Measure Title	Overall Survival (OS)
Measure Description	Overall survival was defined as the time in months from randomization until the date of death. For those patients who had not died, survival duration was censored at the last date the patient was known to be alive. Median OS with 95% CI estimated using the Kaplan-Meier Product Limit Method.
Time Frame	from date of randomization until death
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was conducted on all randomized patients on an intent to treat basis. This study required at least 846 events (deaths) to ensure the 2-sided, α = 0.05 level, log-rank test to have 90% power to show a statistically significant difference in OS between treatment groups when the hazard ratio (HR) is 0.8.

Reporting Groups

	Description
Ixabepilone + Capecitabine	Ixabepilone in combination with capecitabine (combination group): Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each cycle only, plus oral capecitabine 1000 mg/m2 twice a day (BID) (2000 mg/m2 daily dose) x 14 days, followed by 1 week of rest.
Capecitabine	Capecitabine alone: Capecitabine 1250 mg/m2 BID (2500 mg/m2 daily dose) x 14 days, followed by 1 week of rest.

Measured Values

	Ixabepilone + Capecitabine	Capecitabine
Number of Participants Analyzed [units: participants]	609	612
Overall Survival (OS) [units: months] Median ( 95% Confidence Interval )	16.39 ( 14.95 to 17.91 )	15.64 ( 13.86 to 17.02 )

Statistical Analysis 1 for Overall Survival (OS)
Statistical Analysis 2 for Overall Survival (OS)

Measure Type	Secondary
Measure Title	Progression-Free Survival (PFS)
Measure Description	PFS was defined for each patient as the time in months from randomization to the date of progression. Patients who died without a reported prior progression were considered to have progressed on their date of death. Patients who did not progress or die were censored on the date of their last tumor assessment.
Time Frame	every 6 weeks (± 3 days) from randomization while on treatment until documented progression
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients with measurable disease as stratified at the time of randomization; n=480 and n=480 for the 2 treatment groups, respectively. Analysis was conducted once 903 progressions or deaths were observed in 960 participants.

Reporting Groups

	Description
Ixabepilone + Capecitabine	Ixabepilone in combination with capecitabine (combination group): Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each cycle only, plus oral capecitabine 1000 mg/m2 twice a day (BID) (2000 mg/m2 daily dose) x 14 days, followed by 1 week of rest.
Capecitabine	Capecitabine alone: Capecitabine 1250 mg/m2 BID (2500 mg/m2 daily dose) x 14 days, followed by 1 week of rest.

Measured Values

	Ixabepilone + Capecitabine	Capecitabine
Number of Participants Analyzed [units: participants]	480	480
Progression-Free Survival (PFS) [units: months] Median ( 95% Confidence Interval )	6.24 ( 5.59 to 6.77 )	4.40 ( 4.14 to 5.42 )

Statistical Analysis 1 for Progression-Free Survival (PFS)

Measure Type	Secondary
Measure Title	Response Rate (RR)
Measure Description	RR=number of patients in that group whose best response is "partial"(30% decrease in the sum of the longest diameter of target lesions) or "complete" (disappearance of all target lesions), according to the 4-item Response Evaluation Criteria in Solid Tumors (RECIST), divided by the total number of response-evaluable participants
Time Frame	every 6 weeks (± 3 days) from randomization while on treatment until documented progression
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Response-evaluable participants (all treated participants with the correct diagnosis of adenocarcinoma originating in the breast who had measurable disease as determined at baseline).

Reporting Groups

	Description
Ixabepilone + Capecitabine	Ixabepilone in combination with capecitabine (combination group): Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each cycle only, plus oral capecitabine 1000 mg/m2 twice a day (BID) (2000 mg/m2 daily dose) x 14 days, followed by 1 week of rest.
Capecitabine	Capecitabine alone: Capecitabine 1250 mg/m2 BID (2500 mg/m2 daily dose) x 14 days, followed by 1 week of rest.

Measured Values

	Ixabepilone + Capecitabine	Capecitabine
Number of Participants Analyzed [units: participants]	462	462
Response Rate (RR) [units: percentage of participants] Mean ( 95% Confidence Interval )	43.3 ( 38.7 to 47.9 )	28.8 ( 24.7 to 33.2 )

Statistical Analysis 1 for Response Rate (RR)

Measure Type	Secondary
Measure Title	Duration of Response
Measure Description	Measured from the time RECIST criteria (described in previous outcome measure) were first met for "complete" or "partial" response until first date of documented disease progression or death. Patients who neither relapsed nor died were censored on the date of last tumor assessment. Median w/ 95% CI estimated using Kaplan Meier Product Limit Method.
Time Frame	every 6 weeks (± 3 days) from randomization while on treatment until documented progression
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Response-evaluable participants (all treated patients with the correct diagnosis of adenocarcinoma originating in the breast who had measurable disease as determined at baseline)

Reporting Groups

	Description
Ixabepilone + Capecitabine	Ixabepilone in combination with capecitabine (combination group): Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each cycle only, plus oral capecitabine 1000 mg/m2 twice a day (BID) (2000 mg/m2 daily dose) x 14 days, followed by 1 week of rest.
Capecitabine	Capecitabine alone: Capecitabine 1250 mg/m2 BID (2500 mg/m2 daily dose) x 14 days, followed by 1 week of rest.

Measured Values

	Ixabepilone + Capecitabine	Capecitabine
Number of Participants Analyzed [units: participants]	200	133
Duration of Response [units: Months] Median ( 95% Confidence Interval )	6.1 ( 5.5 to 7.0 )	6.3 ( 5.3 to 7.6 )

No statistical analysis provided for Duration of Response

Measure Type	Secondary
Measure Title	Time to Response
Measure Description	Time to response was defined as the time from the first dose of study therapy until measurement criteria were first met for "partial" or "complete" (whichever status was recorded first) per RECIST criteria (a 4-item scale described in the previous outcome measure).
Time Frame	every 6 weeks (± 3 days) from randomization while on treatment until documented progression
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Response-evaluable participants (all treated patients with the correct diagnosis of adenocarcinoma originating in the breast who had measurable disease as determined at baseline)

Reporting Groups

	Description
Ixabepilone + Capecitabine	Ixabepilone in combination with capecitabine (combination group): Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each cycle only, plus oral capecitabine 1000 mg/m2 twice a day (BID) (2000 mg/m2 daily dose) x 14 days, followed by 1 week of rest.
Capecitabine	Capecitabine alone: Capecitabine 1250 mg/m2 BID (2500 mg/m2 daily dose) x 14 days, followed by 1 week of rest.

Measured Values

	Ixabepilone + Capecitabine	Capecitabine
Number of Participants Analyzed [units: participants]	200	133
Time to Response [units: weeks] Median ( Full Range )	6.6 ( 4.7 to 47.9 )	6.6 ( 4.6 to 59.4 )

No statistical analysis provided for Time to Response

Measure Type	Secondary
Measure Title	Treatment-Related Safety Summary
Measure Description	Laboratory values, adverse events, and other symptoms were graded using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTC) Version 3.0
Time Frame	safety was assessed on a continual basis every cycle while on-treatment and every 4 weeks post treatment until toxicities resolved or were deemed irreversible.
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of ixabepilone and/or capecitabine. Participants with baseline hepatic impairment (combination arm, n = 50; capecitabine arm, n = 37), defined as Grade ≥2 AST, ALT or Grade ≥1 total bilirubin, were contraindicated due to disproportionate number of toxic deaths observed in study CA163-046.

Reporting Groups

	Description
Ixabepilone + Capecitabine	Ixabepilone in combination with capecitabine (combination group): Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each cycle only, plus oral capecitabine 1000 mg/m2 twice a day (BID) (2000 mg/m2 daily dose) x 14 days, followed by 1 week of rest.
Capecitabine	Capecitabine alone: Capecitabine 1250 mg/m2 BID (2500 mg/m2 daily dose) x 14 days, followed by 1 week of rest.

Measured Values

	Ixabepilone + Capecitabine	Capecitabine
Number of Participants Analyzed [units: participants]	595	603
Treatment-Related Safety Summary [units: Participants]
Deaths within 30 days of last dose	19	42
Treatment-related serious adverse events	125	64
Treatment-related Grade 3-4 adverse events	458	240
Treatment-related AEs leading to discontinuation	286	66

No statistical analysis provided for Treatment-Related Safety Summary

Measure Type	Secondary
Measure Title	Symptom Assessment Score Changes From Baseline for Functional Assessment of Cancer Therapy-Breast Symptom Index (FBSI)
Measure Description	Quality of life, as measured by the FBSI, an 8-item, participant-reported instrument to measure symptoms. Each item has 5 possible responses ranging from 0 (not at all) to 4 (very much). The scoring was conducted according to the Functional Assessment of Chronic Illness Therapy manual, Version 4; higher scores reflect fewer symptoms.
Time Frame	Baseline and prior to each 21-day cycle of treatment, and at first posttreatment follow-up assessment
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was conducted on all randomized participants on an intent to treat basis. (Note: while table only reports data up to 24 wks, which represents most results, statistical analysis includes ALL assessments through study and follow-up; a few participants were assessed after more than 100 weeks.)

Reporting Groups

	Description
Ixabepilone + Capecitabine	Ixabepilone in combination with capecitabine (combination group): Ixabepilone 40 mg/m2 administered as a 3-hour intravenous (IV) infusion on Day 1 of each cycle only, plus oral capecitabine 1000 mg/m2 twice a day (BID) (2000 mg/m2 daily dose) x 14 days, followed by 1 week of rest.
Capecitabine	Capecitabine alone: Capecitabine 1250 mg/m2 BID (2500 mg/m2 daily dose) x 14 days, followed by 1 week of rest.

Measured Values

	Ixabepilone + Capecitabine	Capecitabine
Number of Participants Analyzed [units: participants]	609	612
Symptom Assessment Score Changes From Baseline for Functional Assessment of Cancer Therapy-Breast Symptom Index (FBSI) [units: units on a scale] Mean ( 95% Confidence Interval )
Week 3 (n=440; n=429)	-0.5 ( -0.96 to 0.20 )	0.0 ( -0.44 to 0.45 )
Week 6 (n=379; n=353)	-0.9 ( -1.45 to -0.31 )	0.5 ( 0.02 to 1.06 )
Week 9 (n=330; n=283)	-1.5 ( -2.15 to -0.79 )	0.7 ( 0.06 to 1.24 )
Week 12 (n=283; n=250)	-1.4 ( -2.06 to -0.64 )	1.1 ( 0.48 to 1.78 )
Week 15 (n=255; n=240)	-1.9 ( -2.73 to -1.15 )	1.5 ( 0.90 to 2.18 )
Week 18 (n=205; n=202)	-1.3 ( -2.07 to -0.50 )	1.2 ( 0.41 to 1.89 )
Week 21 (n=166; n=185)	-1.4 ( -2.36 to -0.37 )	1.7 ( 0.97 to 2.45 )
Week 24 (n=149; n=141)	-1.4 ( -2.46 to -0.41 )	1.1 ( 0.19 to 1.96 )

Statistical Analysis 1 for Symptom Assessment Score Changes From Baseline for Functional Assessment of Cancer Therapy-Breast Symptom Index (FBSI)