Trial Outcomes & Findings for Study of Dose-dense Adriamycin Plus Cytoxan (AC) Followed by Either ABI-007 (Abraxane) or Taxol With Bevacizumab as Adjuvant Therapy for Patients With Breast Cancer (NCT NCT00394251)

Last Updated: 2019-11-25

Results Overview

Toxicities are summarized using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) terms. Participants with treatment-emergent toxicities with a frequency of \>=20% in any treatment arm, and participants with at least one toxicity are reported. Taxane subsets (ABI-007 subset and Taxol subset treatment arms) summarize participants with treatment-emergent toxicities defined as any AEs that begin or worsen in severity grade after the start of taxane treatment (cycle 5, week 9) through 30 days after the last dose of taxane (week 20) and were ongoing 3 months after chemotherapy (month 7). Entire regiments (AC --\> ABI-007 and AC --\> Taxol treatment arms) summarize participants with treatment-emergent toxicities defined as any AEs that begin or worsen in severity grade after the start of chemotherapy (cycle 1, week 1) through 30 days after the last dose of chemotherapy (week 20) and were ongoing 3 months after chemotherapy (month 7).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

197 participants

Primary outcome timeframe

Month 7

Results posted on

2019-11-25

Participant Flow

Multicenter study

Two hundred three patients were randomized and one hundred ninety-seven were treated.

Participant milestones

Participant milestones
Measure	AC --> ABI-007 Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).
Overall Study STARTED	98	99
Overall Study At Least One Dose of Taxane	93	93
Overall Study COMPLETED	61	61
Overall Study NOT COMPLETED	37	38

Reasons for withdrawal

Reasons for withdrawal
Measure	AC --> ABI-007 Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).
Overall Study Adverse Event	7	5
Overall Study Unacceptable Toxicity	20	18
Overall Study Physician Decision	1	1
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	7	11
Overall Study Non-compliance, pt moved, pt/inv agree	2	2

Baseline Characteristics

Study of Dose-dense Adriamycin Plus Cytoxan (AC) Followed by Either ABI-007 (Abraxane) or Taxol With Bevacizumab as Adjuvant Therapy for Patients With Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AC --> ABI-007 n=98 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol n=99 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	Total n=197 Participants Total of all reporting groups
Age, Continuous	51.2 years STANDARD_DEVIATION 9.21 • n=5 Participants	51.2 years STANDARD_DEVIATION 9.29 • n=7 Participants	51.2 years STANDARD_DEVIATION 9.23 • n=5 Participants
Age, Customized >=65 years	9 participants n=5 Participants	11 participants n=7 Participants	20 participants n=5 Participants
Age, Customized < 65 years	89 participants n=5 Participants	88 participants n=7 Participants	177 participants n=5 Participants
Sex: Female, Male Female	98 Participants n=5 Participants	99 Participants n=7 Participants	197 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized White, non-Hispanic, non-Latino	76 participants n=5 Participants	72 participants n=7 Participants	148 participants n=5 Participants
Race/Ethnicity, Customized White, Hispanic or Latino	8 participants n=5 Participants	17 participants n=7 Participants	25 participants n=5 Participants
Race/Ethnicity, Customized Black, of African heritage	10 participants n=5 Participants	7 participants n=7 Participants	17 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment United States	98 participants n=5 Participants	99 participants n=7 Participants	197 participants n=5 Participants
Weight	78.63 kg STANDARD_DEVIATION 19.561 • n=5 Participants	78.78 kg STANDARD_DEVIATION 19.595 • n=7 Participants	78.71 kg STANDARD_DEVIATION 19.528 • n=5 Participants
Menopausal Status premenopausal	50 participants n=5 Participants	44 participants n=7 Participants	94 participants n=5 Participants
Menopausal Status postmenopausal	48 participants n=5 Participants	55 participants n=7 Participants	103 participants n=5 Participants
Stage at Primary Diagnosis I: tumor <=2.0, lymph nodes clear, no metastasis	10 participants n=5 Participants	7 participants n=7 Participants	17 participants n=5 Participants
Stage at Primary Diagnosis IIa: tumor <=2.0 cm, regional lymph node	28 participants n=5 Participants	35 participants n=7 Participants	63 participants n=5 Participants
Stage at Primary Diagnosis IIb: tumor >2.0<5.0cm, regional lymph nodes	32 participants n=5 Participants	24 participants n=7 Participants	56 participants n=5 Participants
Stage at Primary Diagnosis IIIa: tumor may be >5.0 cm, regional lymph nodes	22 participants n=5 Participants	23 participants n=7 Participants	45 participants n=5 Participants
Stage at Primary Diagnosis IIIb: tumor extending to chest wall or skin	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Stage at Primary Diagnosis IIIc: tumor with extensive lymph node involvement	6 participants n=5 Participants	9 participants n=7 Participants	15 participants n=5 Participants
Stage at Primary Diagnosis IV: distant metastasis	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Stage at Primary Diagnosis unknown	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Estrogen Receptor Status Positive	63 participants n=5 Participants	66 participants n=7 Participants	129 participants n=5 Participants
Estrogen Receptor Status Negative	35 participants n=5 Participants	33 participants n=7 Participants	68 participants n=5 Participants
Progesterone Receptor Status Positive	59 participants n=5 Participants	59 participants n=7 Participants	118 participants n=5 Participants
Progesterone Receptor Status Negative	39 participants n=5 Participants	40 participants n=7 Participants	79 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully active)	89 participants n=5 Participants	89 participants n=7 Participants	178 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restrictive but ambulatory)	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants
Physician's Assessment of Peripheral Neuropathy 0 (None)	94 participants n=5 Participants	96 participants n=7 Participants	190 participants n=5 Participants
Physician's Assessment of Peripheral Neuropathy 1	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Physician's Assessment of Peripheral Neuropathy Not reported	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants

PRIMARY outcome

Timeframe: Month 7

Population: Participants in the Treated Population for whom safety data was available 3 months post-chemotherapy

Outcome measures

Outcome measures
Measure	AC --> ABI-007 n=74 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol n=74 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	Taxol Subset n=77 Participants 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	AC --> Taxol n=77 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46).
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy At least 1 AE at 3 Months	65 participants	74 participants	65 participants	77 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy Constitutional Symptoms: Fatigue	16 participants	46 participants	10 participants	32 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy Cardiac General: Hypertension	4 participants	18 participants	7 participants	25 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy Pain: Arthralgia	7 participants	22 participants	8 participants	19 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy Hemorrhage/Bleeding: Nasal	11 participants	19 participants	10 participants	18 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy Neurology: Neuropathy: Sensory	36 participants	50 participants	28 participants	35 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy Dermatology/Skin: Hair Loss/Alopecia (Scalp+Body)	2 participants	33 participants	1 participants	17 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy Endocrine: Hot Flashes/Flushes	12 participants	28 participants	5 participants	22 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy Pain: Other - Extremity	4 participants	15 participants	7 participants	22 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy Pain: Myalgia	10 participants	20 participants	9 participants	16 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy Dermatology/Skin: Nail Changes	14 participants	22 participants	5 participants	10 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy Constitutional Symptoms: Insomnia	3 participants	16 participants	5 participants	11 participants

PRIMARY outcome

Timeframe: Month 10

Population: Participants in the Treated Population for whom safety data was available 6 months post-chemotherapy

Toxicities are summarized using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) terms. Participants with treatment-emergent toxicities with a frequency of \>=20% in any treatment arm, and participants with at least one toxicity are reported. Taxane subsets (ABI-007 subset and Taxol subset treatment arms) summarize participants with treatment-emergent toxicities defined as any AEs that begin or worsen in severity grade after the start of taxane treatment (cycle 5, week 9) through 30 days after the last dose of taxane (week 20) and were ongoing 6 months after chemotherapy (month 10). Entire regiments (AC --\> ABI-007 and AC --\> Taxol treatment arms) summarize participants with treatment-emergent toxicities defined as any AEs that begin or worsen in severity grade after the start of chemotherapy (cycle 1, week 1) through 30 days after the last dose of chemotherapy (week 20) and were ongoing 6 months after chemotherapy (month 10).

Outcome measures

Outcome measures
Measure	AC --> ABI-007 n=63 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol n=63 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	Taxol Subset n=67 Participants 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	AC --> Taxol n=67 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46).
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy At least 1 AE at 6 Months	49 participants	62 participants	46 participants	65 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy Neurology: Neuropathy: Sensory	25 participants	42 participants	15 participants	19 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy Constitutional Symptoms: Fatigue	11 participants	32 participants	4 participants	18 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy Endocrine: Hot Flashes/Flushes	7 participants	23 participants	3 participants	17 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy Cardiac General: Hypertension	4 participants	12 participants	7 participants	18 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy Pain: Arthralgia	4 participants	17 participants	3 participants	13 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy Pain: Myalgia	8 participants	17 participants	4 participants	8 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy Pain: Other - Extremity	1 participants	6 participants	5 participants	14 participants
Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy Dermatology/Skin: Nail Changes	8 participants	13 participants	3 participants	6 participants

SECONDARY outcome

Timeframe: approximately week 9-16

Population: Participants in the treated population who received at least 1 dose of taxane.

The cumulative dose of taxane (Taxol or ABI-007) taken during the study (cycles 4-8 which is approximately weeks 9-16).

Outcome measures

Outcome measures
Measure	AC --> ABI-007 n=93 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol n=93 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	Taxol Subset 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	AC --> Taxol Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46).
The Cumulative Dose of Taxane Delivered During Study	950.5 mg/m^2 Standard Deviation 199.86	660.8 mg/m^2 Standard Deviation 99.52	—	—

SECONDARY outcome

Timeframe: approximately week 9-16

Population: Participants in the treated population who received at least 1 dose of taxane.

Cumulative taxane (ABI-007 or Taxol) dose divided by the number of weeks on taxane treatment.

Outcome measures

Outcome measures
Measure	AC --> ABI-007 n=93 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol n=93 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	Taxol Subset 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	AC --> Taxol Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46).
Mean Taxane Dose Intensity Per Week	118.82 mg/m^2/week Standard Deviation 24.983	82.60 mg/m^2/week Standard Deviation 12.440	—	—

SECONDARY outcome

Timeframe: approximately week 9-16

Population: Participants in the treated population who received at least 1 dose of taxane.

Percent of the protocol-defined taxane (ABI-007 or Taxol) dose that was actually taken by study participants.

Outcome measures

Outcome measures
Measure	AC --> ABI-007 n=93 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol n=93 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	Taxol Subset 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	AC --> Taxol Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46).
Percent of Protocol Taxane Dose	91.40 percentage of protocol-defined taxane Standard Deviation 19.218	94.40 percentage of protocol-defined taxane Standard Deviation 14.217	—	—

SECONDARY outcome

Timeframe: up to Week 46

Population: Treated population

Counts of participants who * completed the protocol-defined treatment cycles, * had a dose interruption * had a dose reduction * had a dose delay. A dose delay refers to the delay of all interventions in the cycle. Dose modifications are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities. Use of pegfilgrastim is included in the summary.

Outcome measures

Outcome measures
Measure	AC --> ABI-007 n=98 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol n=99 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	Taxol Subset 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	AC --> Taxol Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46).
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays One or more dose interruption: Cytoxan	3 participants	1 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays One or more dose interruption: Bevacizumab	0 participants	2 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays Completed 4 cycles of Adriamycin/Cytoxan (AC)	95 participants	95 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays Received pegfilgrastim for 4 cycles during AC	95 participants	94 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays Completed 4 cycles of taxane	82 participants	84 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays Completed 18 cycles of bevacizumab	61 participants	61 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays One or more dose reduction: Adriamycin	10 participants	6 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays One or more dose reduction: Cytoxan	9 participants	5 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays One or more dose reduction: Taxane	12 participants	16 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays One or more dose interruption: Adriamycin	1 participants	0 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays One or more dose interruption: Taxane	0 participants	3 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays One or more delay in study regimen	50 participants	48 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays Discontinued pegfilgrastim during AC cycles	0 participants	0 participants	—	—
Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays Administered pegfilgrastim during taxane cycles	23 participants	13 participants	—	—

SECONDARY outcome

Timeframe: Weeks 9-16

Population: Participants in the treated population who received at least 1 dose of taxane and had laboratory values.

Myelosuppression represented by neutropenia (low absolute neutrophil counts (ANC)) with severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE). * Grade 1 = \<lower limit of normal (LLN)-1.5\*10\^9/L * Grade 2 = \<1.5 - 1.0\*10\^9/L * Grade 3 = \<1.0 - 0.5\*10\^9/L * Grade 4 = \<0.5\*10\^9/L Values are reported across all severity grades without assessment of relationship to taxane treatment, and also by relation to taxane treatment as reported by investigators.

Outcome measures

Outcome measures
Measure	AC --> ABI-007 n=92 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol n=93 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	Taxol Subset 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	AC --> Taxol Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46).
Myelosuppression During Taxane Dosing Cycles Taxane-related, grades 3-4	6 participants	5 participants	—	—
Myelosuppression During Taxane Dosing Cycles ANC (grades 1-4)	58 participants	43 participants	—	—
Myelosuppression During Taxane Dosing Cycles Taxane-related, grades 1-4	11 participants	8 participants	—	—

SECONDARY outcome

Timeframe: up to week 46

Population: Participants in the treated population who had both baseline and one treatment measurement for %LVEF

Decreased left ventricular ejection fraction (LVEF) is an indication of cardiotoxicity. Change from baseline measurements to the final evaluation are summarized.

Outcome measures

Outcome measures
Measure	AC --> ABI-007 n=95 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol n=92 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	Taxol Subset 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	AC --> Taxol Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46).
Change From Baseline in Percent Left Ventricular Ejection Fraction (% LVEF) at the Final Evaluation	-1.0 percentage of healthy LVEF Full Range 7.40 • Interval -30.0 to 16.0	-1.0 percentage of healthy LVEF Full Range 93.40 • Interval -699.0 to 16.0	—	—

SECONDARY outcome

Timeframe: Week 1 up to week 50

Population: Treated population with at least one post-treatment laboratory measure.

Summary of the most severe grades using the National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0 (CTCAE) for the following liver and renal function tests. Grade 0 = within normal range for all measurements. Alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST): * Grade 1 = \> upper limit of normal (ULN) - 2.5\*ULN * Grade 2= \>2.5-5.0\*ULN * Grade 3= \>5.0-20.0\*ULN * Grade 4= \>20.0\*ULN Bilirubin: * Grade 1= \>ULN - 1.5\*ULN * Grade 3= \>3.0 - 10.0\*ULN Creatinine: \- Grade 1= \>ULN - 1.5\*ULN

Outcome measures

Outcome measures
Measure	AC --> ABI-007 n=96 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol n=99 Participants Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	Taxol Subset 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	AC --> Taxol Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46).
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) Alkaline phosphatase, Grade 0	69 participants	70 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) Alkaline phosphatase, Grade 1	26 participants	29 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) Alkaline phosphatase, Grade 2	1 participants	0 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) ALT, Grade 0	66 participants	75 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) ALT, Grade 1	24 participants	23 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) ALT, Grade 2	5 participants	1 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) ALT, Grade 4	1 participants	0 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) AST, grade 0	74 participants	81 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) AST, grade 1	20 participants	17 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) AST, grade 2	1 participants	1 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) AST, grade 3	1 participants	0 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) Bilirubin, grade 0	95 participants	98 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) Bilirubin, grade 1	0 participants	1 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) Bilirubin, grade 3	1 participants	0 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) Creatinine, grade 0	94 participants	97 participants	—	—
Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) Creatinine, grade 1	2 participants	2 participants	—	—

Adverse Events

AC --> ABI-007

Serious events: 30 serious events

Other events: 97 other events

Deaths: 0 deaths

AC --> Taxol

Serious events: 21 serious events

Other events: 99 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Associate Director, Clinical Trials Disclosure

Celgene Corporation

Phone: 1-888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it has been more than 2 years since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decided publication would hinder patent applications, Investigator must delay submission for up to 1 year. Investigator must delete confidential information before submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	AC --> ABI-007 n=98 participants at risk Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).	AC --> Taxol n=99 participants at risk Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).
Gastrointestinal disorders Appendicitis perforated	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Musculoskeletal and connective tissue disorders Arthralgia	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Cardiac disorders Cardiac failure	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Cardiac disorders Cardiac failure congestive	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	4.0% 4/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
General disorders Chest pain	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	2.0% 2/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Blood and lymphatic system disorders Coagulopathy	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Gastrointestinal disorders Colitis	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Diverticulitis	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Blood and lymphatic system disorders Febrile neutropenia	7.1% 7/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	5.1% 5/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Vascular disorders Hypertension	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Vascular disorders Hypotension	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Gastrointestinal disorders Ileus	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Cardiac disorders Pericardial effusion	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Perirectal abscess	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Pneumonia	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
General disorders Pyrexia	2.0% 2/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Sepsis	2.0% 2/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Sinusitis	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Wound infection	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Metabolism and nutrition disorders Hyponatraemia	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Metabolism and nutrition disorders Hypovolaemia	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Injury, poisoning and procedural complications Wound dehiscence	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Skin and subcutaneous tissue disorders Skin reaction	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Cellulitis	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Appendicitis	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Breast cellulitis	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Catheter related infection	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Catheter site cellulitis	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Gastroenteritis	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Postoperative wound infection	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Staphylococcal sepsis	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Infections and infestations Urinary tract infection	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Blood and lymphatic system disorders Pancytopenia	2.0% 2/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
General disorders Non-cardiac chest pain	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Gastrointestinal disorders Abdominal pain upper	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Gastrointestinal disorders Oesophagitis ulcerative	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Nervous system disorders Syncope	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	2.0% 2/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Nervous system disorders Cerebrovascular accident	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Nervous system disorders Encephalopathy	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Vascular disorders Deep vein thrombosis	2.0% 2/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Musculoskeletal and connective tissue disorders Bone pain	1.0% 1/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	0.00% 0/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Metabolism and nutrition disorders Dehydration	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Investigations Hepatic enzyme increased	0.00% 0/98 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)	1.0% 1/99 • Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)