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

• Sponsor: Celgene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00394251
• Collaborator: (none)
• Enrollment: 197
• Locations: 27
• Arms: 2
• Actual Duration (Months): 18
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary objective of this study was to compare the safety of dose-dense ABI-007 (Abraxane) 260 mg/m^{2 or Taxol 175 mg/m}2 given every 2 weeks following dose-dense Adriamycin plus Cytoxan (AC) chemotherapy. Bevacizumab was administered at 10 mg/kg every 2 weeks throughout chemotherapy, and then at 15 mg/kg every 3 weeks following chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Adriamycin and Cytoxan (AC); Drug: ABI-007; Drug: Taxol; Drug: Bevacizumab; Drug: pegfilgrastim	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 197 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomized, Comparative Pilot 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
• Actual Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Mar 1, 2007
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	Drug: Adriamycin and Cytoxan (AC); Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) make up the chemotherapy regimen known as AC. Adriamycin 60 mg/m^2 intravenous, plus Cytoxan 600 mg/m^2 intravenous on Day 1 of each of four 2-week cycles (weeks 1-8).; Other Names: doxorubicin cyclophosphamide ; Drug: ABI-007; 260 mg/m^2 IV on day 1 of each of four 2-week cycle, representing treatment cycles 5-8 (weeks 9-16); Other Names: Abraxane ; Drug: Bevacizumab; 10 mg/kg on day 1 of each of eight 2-week cycles (weeks 9-16), then 15 mg/kg on day 1 of each of ten three-week cycles (weeks 17-46).; Other Names: Avastin® ; Drug: pegfilgrastim; 6 mg subcutaneous (SC) on day 2 for each of the first four 2-week cycles (weeks 1-8). Pegfilgrastim 6 mg SC was administered on day 2 of cycles 6-8 (weeks 11-16) during taxane treatment only if necessary.; Other Names: Neulasta
Experimental: 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).	Drug: Adriamycin and Cytoxan (AC); Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) make up the chemotherapy regimen known as AC. Adriamycin 60 mg/m^2 intravenous, plus Cytoxan 600 mg/m^2 intravenous on Day 1 of each of four 2-week cycles (weeks 1-8).; Other Names: doxorubicin cyclophosphamide ; Drug: Taxol; 175 mg/m^2 intravenously (IV) on day 1 of each of four 2-week cycle, representing treatment cycles 5-8 (weeks 9-16); Other Names: paclitaxel ; Drug: Bevacizumab; 10 mg/kg on day 1 of each of eight 2-week cycles (weeks 9-16), then 15 mg/kg on day 1 of each of ten three-week cycles (weeks 17-46).; Other Names: Avastin® ; Drug: pegfilgrastim; 6 mg subcutaneous (SC) on day 2 for each of the first four 2-week cycles (weeks 1-8). Pegfilgrastim 6 mg SC was administered on day 2 of cycles 6-8 (weeks 11-16) during taxane treatment only if necessary.; Other Names: Neulasta

Outcome Measures

Primary Outcome Measures

1. Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy [Month 7]

   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).

2. Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy [Month 10]

   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).

Secondary Outcome Measures

1. The Cumulative Dose of Taxane Delivered During Study [approximately week 9-16]

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

2. Mean Taxane Dose Intensity Per Week [approximately week 9-16]

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

3. Percent of Protocol Taxane Dose [approximately week 9-16]

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

4. Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays [up to Week 46]

   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.

5. Myelosuppression During Taxane Dosing Cycles [Weeks 9-16]

   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.

6. Change From Baseline in Percent Left Ventricular Ejection Fraction (% LVEF) at the Final Evaluation [up to week 46]

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

7. Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles) [Week 1 up to week 50]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

A patient was eligible for inclusion in this study only if all of the following criteria were met:

1. Female, age greater than or equal to 18 to less than or equal to 70 years old.

2. Estrogen receptor (ER) and progesterone receptor (PR) status have been determined.

3. Operable, histologically confirmed adenocarcinoma of the breast

4. Must have met 1 of the following criteria:

• T1-3, N1-3, M0, regardless of ER or PR status.

• T > 2 cm, N0, M0 (T2-3N0M0), regardless of ER or PR status.

• T > 1 cm, N0, M0 (T1cN0M0) and both ER and PR negative

• T > 1 cm, N0, M0, ER or PR positive and grade 3

1. Patients with one sentinel lymph node metastasis 0.2-2 mm in size were not required to undergo completion axillary dissection unless only 1 sentinel lymph node was examined. This completion axillary dissection was optional if 1 out of 2 or more sentinel lymph nodes was positive for a micrometastasis. Therefore if 1 of 1 sentinel lymph node was positive for micrometastasis(0.2-2 mm), then a completion axillary dissection was required.

2. Patients with more than one sentinel node micrometastasis or 1 node with a micrometastasis > 2 mm and/or T3 disease must have undergone completion, standard axillary dissection. -Note: the following were not eligible-

T1b,c,N0M0 and ER or PR positive and grade 1 or 2 Tx tumors (regardless of nodal status) T4 disease [i.e., patients with fixed tumors, peau d'orange skin changes, skin ulcerations, or inflammatory changes

• Note: Sentinel lymph node micrometastasis < 0.2 mm in considered N0 disease

1. Negative surgical margins on lumpectomy or mastectomy specimen (no ink on invasive cancer and no ink on ductal carcinoma in situ [DCIS]).

2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

3. Normal electrocardiogram (ECG, as assessed by the investigator).

4. No pre-existing peripheral neuropathy.

5. It had not been longer than 84 days since the date of definitive surgery (eg, mastectomy or in the case of a breast-sparing procedure, axillary dissection).

6. Laboratory values were to be as follows:

• White blood cell count: > or equal to 3,000/mm^3

• Absolute neutrophil count:> or equal to 1,500/mm^3

• Platelets:> or equal to 100,000/mm^3

• Hemoglobin: > or equal to 8g/dL

• Bilirubin:< or equal to the institution's ULN

• Creatinine: < or equal to 1.7 mg/dL

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and alkaline phosphatase could be up to 2.5 times the institutional ULN.

1. All staging studies including physical exam, chest x-ray, and bone scan had to show no evidence of metastatic disease, including suspicious lymphadenopathy or skin nodules on physical exam. A chest x-ray and bone scan were mandatory; however, all other staging studies were at the treating physician's discretion. Any other staging test (eg, Computed Tomography [CT] scans, magnetic resonance imaging [MRI] studies, ultrasound of abdomen, Positron Emission Tomography [PET] scans must have been negative for metastatic disease. An abdominal CT scan or PET scan was mandatory for patients with liver function tests elevated above the upper limit of normal (ULN) to rule out metastatic disease. If the patient had a staging PET scan then a bone scan was not necessary, but a chest x-ray was required.

2. Patient had a negative serum pregnancy test < or equal to 14 days of the first dose of study drug (patients of childbearing potential).

3. If fertile, patient had agreed to us an acceptable method of birth control to avoid pregnancy [Note: oral contraceptives were not allowed] for the duration of chemotherapy and hormonal therapy and for 6 months thereafter.

4. If obese, a patient must have been treated with doses calculated using his/her actual body surface area (BSA) (the physician must have been comfortable treating at the full BSA dose regardless of BSA).

5. Patient had signed a Patient Informed Consent Form.

Exclusion Criteria:

A patient was not eligible for inclusion in this study if any of the following criteria applied:

1. Patients with HER-2 positive breast cancer (IHC 3+ or FISH +) who were eligible for adjuvant Herceptin therapy.

2. Stage IV breast cancer (M1 disease on TNM staging system).

3. Prior anthracycline, anthracenedione (mitoxantrone), or taxane therapy

4. Neoadjuvant therapy for this breast cancer.

5. Previous invasive cancers if treated < 5 years prior to entering this study, except basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; the latter were not required to have occurred more than 5 years prior to study entry.

6. Prior invasive breast cancer if diagnosed < 5 years prior to entering study. Patients must have finished adjuvant hormonal therapy prior to registration. Patients with prior DCIS are eligible. Patients with DCIS who were treated with tamoxifen must have finished tamoxifen prior to registration.

7. Serious medical illness, other than that treated by this study, which would limit survival to < 4 years, or psychiatric condition that would prevent informed consent and compliance with study treatment.

8. Uncontrolled or severe cardiovascular disease including recent (< or equal to 12 months) myocardial infarction or unstable angina.

9. Active uncontrolled bacterial, viral (including clinically defined Acquired Immune Deficiency Syndrome [AIDS]), or fungal infection.

10. Patients with active or chronic hepatitis with abnormal liver function tests (LFTs) or patients who were known to be HIV positive.

11. Uncontrolled disease such as uncontrolled diabetes.

12. Any prior history of hypertensive crisis or hypertensive encephalopathy.

13. Any known central nervous system (CNS) disease.

14. Known hypersensitivity to any component of bevacizumab.

15. No history of cerebrovascular accident or transient ischemic attack at any time.

16. Active symptomatic vascular disease, e.g., aortic aneurysm or aortic dissection, and no peripheral vascular disease, e.g., claudication, within six months of study entry.

17. No major surgical procedure, open biopsy, or significant traumatic injury within 28 days and no core biopsy or minor surgical procedure (excluding placement of a vascular access device) within seven days of study entry. No anticipated need for major surgical procedure during the course of study.

18. No history of abdominal fistula, gastrointestinal perforation, or intra- abdominal process within six months of study entry.

19. No serious non-healing wound, ulcer, or bone fracture.

20. No proteinuria at screening as demonstrated by urine protein: urine creatinine (UPC) ratio of > or equal to 1.0 or urine dipstick for proteinuria > or equal to 2+ (patients discovered to have > or equal to 2+ proteinuria on dipstick urinalysis at baseline should have undergone a 24 hour urine collection and must have demonstrated < or equal to 1g of protein in 24 hours to be eligible).

21. Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and /or diastolic blood pressure> 100 mmHg on antihypertensive medications) or New York Heart Association (NYHA) Grade 2 or greater congestive heart failure.

22. History or coagulopathy, bleeding diathesis, therapeutic anticoagulation other than low dose or chronic acetyl salicylic acid (ASA)> or equal to 325 mg. per day. Low dose coumadin for anticoagulation of venous access device or low dose molecular weight heparin (LMWH) for deep vein thrombosis prophylaxis or low dose (325 mg or less) ASA prophylaxis are allowed, but are best avoided if the treating physician feels it is safe to do so.

23. Left Ventricular Ejection Fraction (LVEF) on cardiac echocardiography (ECHO) < 50% (or institutional lower limit of normal [LLN]) and > or equal to 74%. LVEF of greater than 75% at baseline should have been re- reviewed and/or the test repeated as it could be falsely elevated.

24. Patients who were receiving concurrent immunotherapy.

25. A history of other malignancy within the last 5 years, which could affect the diagnosis or assessment of breast cancer recurrence or which could shorten a patient's survival.

26. Patient had had an organ allograft.

27. Patient was pregnant or breastfeeding.

28. Patient was unable to comply with requirements of study.

29. Patient was receiving any other investigational drugs.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35205
2		Sedona	Arizona	United States	86336
3		Denver	Colorado	United States	80220
4		Torrington	Connecticut	United States	06790
5		Indianapolis	Indiana	United States	46227
6		Minneapolis	Minnesota	United States	55404
7		Columbia	Missouri	United States	65201
8		Saint Louis	Missouri	United States	63136
9		Henderson	Nevada	United States	89052
10		Raleigh	North Carolina	United States	27607
11		Eugene	Oregon	United States	97401
12		Greenville	South Carolina	United States	29615
13		Austin	Texas	United States	78731
14		Bedford	Texas	United States	76022
15		Dallas	Texas	United States	75231
16		Dallas	Texas	United States	75246
17		El Paso	Texas	United States	79915
18		Fort Worth	Texas	United States	76104
19		Fredericksburg	Texas	United States	78624
20		Houston	Texas	United States	77024
21		Longview	Texas	United States	75601
22		McAllen	Texas	United States	78503
23		Tyler	Texas	United States	75702
24		Waco	Texas	United States	76712
25		Fairfax	Virginia	United States	22031
26		Norfolk	Virginia	United States	23502
27		Vancouver	Washington	United States	98684

Sponsors and Collaborators

• Celgene

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT00394251
• Other Study ID Numbers: CA045
• First Posted: Oct 31, 2006
• Last Update Posted: Nov 25, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Celgene: Adjuvant therapy; Bevacizumab; Abraxane; Early stage breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Cyclophosphamide; Bevacizumab; Doxorubicin; Liposomal doxorubicin; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Recruitment Details	Multicenter study
Pre-assignment Detail	Two hundred three patients were randomized and one hundred ninety-seven were treated.

Arm/Group Title	AC --> ABI-007	AC --> Taxol
Arm/Group Description	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).	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).
Period Title: Overall Study
STARTED	98	99
At Least One Dose of Taxane	93	93
COMPLETED	61	61
NOT COMPLETED	37	38

Baseline Characteristics

Arm/Group Title	AC --> ABI-007	AC --> Taxol	Total
Arm/Group Description	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).	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 of all reporting groups
Overall Participants	98	99	197
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.2 (9.21)	51.2 (9.29)	51.2 (9.23)
Age, Customized (participants) [Number]
>=65 years	9 9.2%	11 11.1%	20 10.2%
< 65 years	89 90.8%	88 88.9%	177 89.8%
Sex: Female, Male (Count of Participants)
Female	98 100%	99 100%	197 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Asian	3 3.1%	2 2%	5 2.5%
White, non-Hispanic, non-Latino	76 77.6%	72 72.7%	148 75.1%
White, Hispanic or Latino	8 8.2%	17 17.2%	25 12.7%
Black, of African heritage	10 10.2%	7 7.1%	17 8.6%
Other	1 1%	1 1%	2 1%
Region of Enrollment (participants) [Number]
United States	98 100%	99 100%	197 100%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	78.63 (19.561)	78.78 (19.595)	78.71 (19.528)
Menopausal Status (participants) [Number]
premenopausal	50 51%	44 44.4%	94 47.7%
postmenopausal	48 49%	55 55.6%	103 52.3%
Stage at Primary Diagnosis (participants) [Number]
I: tumor <=2.0, lymph nodes clear, no metastasis	10 10.2%	7 7.1%	17 8.6%
IIa: tumor <=2.0 cm, regional lymph node	28 28.6%	35 35.4%	63 32%
IIb: tumor >2.0<5.0cm, regional lymph nodes	32 32.7%	24 24.2%	56 28.4%
IIIa: tumor may be >5.0 cm, regional lymph nodes	22 22.4%	23 23.2%	45 22.8%
IIIb: tumor extending to chest wall or skin	0 0%	0 0%	0 0%
IIIc: tumor with extensive lymph node involvement	6 6.1%	9 9.1%	15 7.6%
IV: distant metastasis	0 0%	0 0%	0 0%
unknown	0 0%	1 1%	1 0.5%
Estrogen Receptor Status (participants) [Number]
Positive	63 64.3%	66 66.7%	129 65.5%
Negative	35 35.7%	33 33.3%	68 34.5%
Progesterone Receptor Status (participants) [Number]
Positive	59 60.2%	59 59.6%	118 59.9%
Negative	39 39.8%	40 40.4%	79 40.1%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
0 (Fully active)	89 90.8%	89 89.9%	178 90.4%
1 (Restrictive but ambulatory)	9 9.2%	10 10.1%	19 9.6%
Physician's Assessment of Peripheral Neuropathy (participants) [Number]
0 (None)	94 95.9%	96 97%	190 96.4%
1	1 1%	0 0%	1 0.5%
Not reported	3 3.1%	3 3%	6 3%

Outcome Measures

1. Secondary Outcome

Title	The Cumulative Dose of Taxane Delivered During Study
Description	The cumulative dose of taxane (Taxol or ABI-007) taken during the study (cycles 4-8 which is approximately weeks 9-16).
Time Frame	approximately week 9-16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	AC --> ABI-007	AC --> Taxol
Arm/Group Description	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).	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).
Measure Participants	93	93
Mean (Standard Deviation) [mg/m^2]	950.5 (199.86)	660.8 (99.52)

2. Secondary Outcome

Title	Mean Taxane Dose Intensity Per Week
Description	Cumulative taxane (ABI-007 or Taxol) dose divided by the number of weeks on taxane treatment.
Time Frame	approximately week 9-16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	AC --> ABI-007	AC --> Taxol
Arm/Group Description	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).	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).
Measure Participants	93	93
Mean (Standard Deviation) [mg/m^2/week]	118.82 (24.983)	82.60 (12.440)

3. Primary Outcome

Title	Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 3 Months Post Chemotherapy
Description	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).
Time Frame	Month 7

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	ABI-007 Subset	AC --> ABI-007	Taxol Subset	AC --> Taxol
Arm/Group Description	260 mg/m2 ABI-007 (Abraxane) plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m2 ABI-007 (Abraxane) plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46).	175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	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).
Measure Participants	74	74	77	77
At least 1 AE at 3 Months	65 66.3%	74 74.7%	65 33%	77 NaN
Neurology: Neuropathy: Sensory	36 36.7%	50 50.5%	28 14.2%	35 NaN
Constitutional Symptoms: Fatigue	16 16.3%	46 46.5%	10 5.1%	32 NaN
Dermatology/Skin: Hair Loss/Alopecia (Scalp+Body)	2 2%	33 33.3%	1 0.5%	17 NaN
Endocrine: Hot Flashes/Flushes	12 12.2%	28 28.3%	5 2.5%	22 NaN
Cardiac General: Hypertension	4 4.1%	18 18.2%	7 3.6%	25 NaN
Pain: Arthralgia	7 7.1%	22 22.2%	8 4.1%	19 NaN
Hemorrhage/Bleeding: Nasal	11 11.2%	19 19.2%	10 5.1%	18 NaN
Pain: Other - Extremity	4 4.1%	15 15.2%	7 3.6%	22 NaN
Pain: Myalgia	10 10.2%	20 20.2%	9 4.6%	16 NaN
Dermatology/Skin: Nail Changes	14 14.3%	22 22.2%	5 2.5%	10 NaN
Constitutional Symptoms: Insomnia	3 3.1%	16 16.2%	5 2.5%	11 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AC --> ABI-007, Taxol Subset
	Comments	Comparison of percentage of participants with at least one taxane-emergent toxicity
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.641
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Percent of Protocol Taxane Dose
Description	Percent of the protocol-defined taxane (ABI-007 or Taxol) dose that was actually taken by study participants.
Time Frame	approximately week 9-16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	AC --> ABI-007	AC --> Taxol
Arm/Group Description	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).	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).
Measure Participants	93	93
Mean (Standard Deviation) [percentage of protocol-defined taxane]	91.40 (19.218)	94.40 (14.217)

5. Secondary Outcome

Title	Summary of Participant Treatment Exposure, Dose Interruptions, Dose Reductions, and Dose Delays
Description	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.
Time Frame	up to Week 46

Outcome Measure Data

Analysis Population Description

Treated population

Arm/Group Title	AC --> ABI-007	AC --> Taxol
Arm/Group Description	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).	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).
Measure Participants	98	99
Completed 4 cycles of Adriamycin/Cytoxan (AC)	95 96.9%	95 96%
Received pegfilgrastim for 4 cycles during AC	95 96.9%	94 94.9%
Completed 4 cycles of taxane	82 83.7%	84 84.8%
Completed 18 cycles of bevacizumab	61 62.2%	61 61.6%
One or more dose reduction: Adriamycin	10 10.2%	6 6.1%
One or more dose reduction: Cytoxan	9 9.2%	5 5.1%
One or more dose reduction: Taxane	12 12.2%	16 16.2%
One or more dose interruption: Adriamycin	1 1%	0 0%
One or more dose interruption: Cytoxan	3 3.1%	1 1%
One or more dose interruption: Taxane	0 0%	3 3%
One or more dose interruption: Bevacizumab	0 0%	2 2%
One or more delay in study regimen	50 51%	48 48.5%
Discontinued pegfilgrastim during AC cycles	0 0%	0 0%
Administered pegfilgrastim during taxane cycles	23 23.5%	13 13.1%

6. Secondary Outcome

Title	Myelosuppression During Taxane Dosing Cycles
Description	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.
Time Frame	Weeks 9-16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	AC --> ABI-007	AC --> Taxol
Arm/Group Description	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).	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).
Measure Participants	92	93
ANC (grades 1-4)	58 59.2%	43 43.4%
Taxane-related, grades 1-4	11 11.2%	8 8.1%
Taxane-related, grades 3-4	6 6.1%	5 5.1%

7. Secondary Outcome

Title	Change From Baseline in Percent Left Ventricular Ejection Fraction (% LVEF) at the Final Evaluation
Description	Decreased left ventricular ejection fraction (LVEF) is an indication of cardiotoxicity. Change from baseline measurements to the final evaluation are summarized.
Time Frame	up to week 46

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	AC --> ABI-007	AC --> Taxol
Arm/Group Description	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).	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).
Measure Participants	95	92
Median (Full Range) [percentage of healthy LVEF]	-1.0 (7.40)	-1.0 (93.40)

8. Secondary Outcome

Title	Summary of Participants' Most Severe Grade for Liver and Renal Function Laboratory Adverse Experiences During Study (All Treatment Cycles)
Description	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
Time Frame	Week 1 up to week 50

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	AC --> ABI-007	AC --> Taxol
Arm/Group Description	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).	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).
Measure Participants	96	99
Alkaline phosphatase, Grade 0	69 70.4%	70 70.7%
Alkaline phosphatase, Grade 1	26 26.5%	29 29.3%
Alkaline phosphatase, Grade 2	1 1%	0 0%
ALT, Grade 0	66 67.3%	75 75.8%
ALT, Grade 1	24 24.5%	23 23.2%
ALT, Grade 2	5 5.1%	1 1%
ALT, Grade 4	1 1%	0 0%
AST, grade 0	74 75.5%	81 81.8%
AST, grade 1	20 20.4%	17 17.2%
AST, grade 2	1 1%	1 1%
AST, grade 3	1 1%	0 0%
Bilirubin, grade 0	95 96.9%	98 99%
Bilirubin, grade 1	0 0%	1 1%
Bilirubin, grade 3	1 1%	0 0%
Creatinine, grade 0	94 95.9%	97 98%
Creatinine, grade 1	2 2%	2 2%

9. Primary Outcome

Title	Participants With Treatment-Emergent Toxicities With a Frequency >=20% at 6 Months Post Chemotherapy
Description	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).
Time Frame	Month 10

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	ABI-007 Subset	AC --> ABI-007	Taxol Subset	AC --> Taxol
Arm/Group Description	260 mg/m2 ABI-007 (Abraxane) plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m2 ABI-007 (Abraxane) plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46).	175 mg/m2 Taxol plus Bevacizumab for 4 cycles (weeks 9-16); Bevacizumab (weeks 17-46). Weeks 1-8 are excluded from this subset.	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).
Measure Participants	63	63	67	67
At least 1 AE at 6 Months	49 50%	62 62.6%	46 23.4%	65 NaN
Neurology: Neuropathy: Sensory	25 25.5%	42 42.4%	15 7.6%	19 NaN
Constitutional Symptoms: Fatigue	11 11.2%	32 32.3%	4 2%	18 NaN
Endocrine: Hot Flashes/Flushes	7 7.1%	23 23.2%	3 1.5%	17 NaN
Cardiac General: Hypertension	4 4.1%	12 12.1%	7 3.6%	18 NaN
Pain: Arthralgia	4 4.1%	17 17.2%	3 1.5%	13 NaN
Pain: Myalgia	8 8.2%	17 17.2%	4 2%	8 NaN
Pain: Other - Extremity	1 1%	6 6.1%	5 2.5%	14 NaN
Dermatology/Skin: Nail Changes	8 8.2%	13 13.1%	3 1.5%	6 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AC --> ABI-007, Taxol Subset
	Comments	Comparison of percentage of participants with at least one taxane-emergent toxicity
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.323
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Day 1 - up to week 50 (weeks 1-46 treatment, plus 30 days after last study dose)
Arm/Group Title	AC --> ABI-007		AC --> Taxol
Arm/Group Description	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).		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).
All Cause Mortality
	AC --> ABI-007		AC --> Taxol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AC --> ABI-007		AC --> Taxol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/98 (30.6%)		21/99 (21.2%)
Blood and lymphatic system disorders
Coagulopathy	1/98 (1%)		0/99 (0%)
Febrile neutropenia	7/98 (7.1%)		5/99 (5.1%)
Pancytopenia	2/98 (2%)		0/99 (0%)
Cardiac disorders
Cardiac failure	0/98 (0%)		1/99 (1%)
Cardiac failure congestive	0/98 (0%)		4/99 (4%)
Pericardial effusion	0/98 (0%)		1/99 (1%)
Gastrointestinal disorders
Appendicitis perforated	1/98 (1%)		0/99 (0%)
Colitis	1/98 (1%)		0/99 (0%)
Ileus	1/98 (1%)		0/99 (0%)
Abdominal pain upper	1/98 (1%)		0/99 (0%)
Gastrointestinal haemorrhage	0/98 (0%)		1/99 (1%)
Oesophagitis ulcerative	0/98 (0%)		1/99 (1%)
General disorders
Chest pain	1/98 (1%)		2/99 (2%)
Pyrexia	2/98 (2%)		0/99 (0%)
Non-cardiac chest pain	1/98 (1%)		0/99 (0%)
Infections and infestations
Diverticulitis	1/98 (1%)		1/99 (1%)
Perirectal abscess	1/98 (1%)		0/99 (0%)
Pneumonia	1/98 (1%)		1/99 (1%)
Sepsis	2/98 (2%)		0/99 (0%)
Sinusitis	1/98 (1%)		0/99 (0%)
Wound infection	1/98 (1%)		0/99 (0%)
Cellulitis	1/98 (1%)		1/99 (1%)
Appendicitis	1/98 (1%)		0/99 (0%)
Breast cellulitis	0/98 (0%)		1/99 (1%)
Catheter related infection	0/98 (0%)		1/99 (1%)
Catheter site cellulitis	1/98 (1%)		0/99 (0%)
Gastroenteritis	0/98 (0%)		1/99 (1%)
Postoperative wound infection	0/98 (0%)		1/99 (1%)
Staphylococcal sepsis	1/98 (1%)		0/99 (0%)
Urinary tract infection	0/98 (0%)		1/99 (1%)
Injury, poisoning and procedural complications
Wound dehiscence	1/98 (1%)		1/99 (1%)
Investigations
Hepatic enzyme increased	0/98 (0%)		1/99 (1%)
Metabolism and nutrition disorders
Hyponatraemia	1/98 (1%)		0/99 (0%)
Hypovolaemia	1/98 (1%)		0/99 (0%)
Dehydration	0/98 (0%)		1/99 (1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/98 (1%)		1/99 (1%)
Myalgia	0/98 (0%)		1/99 (1%)
Bone pain	1/98 (1%)		0/99 (0%)
Nervous system disorders
Syncope	1/98 (1%)		2/99 (2%)
Cerebrovascular accident	1/98 (1%)		0/99 (0%)
Encephalopathy	0/98 (0%)		1/99 (1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/98 (1%)		0/99 (0%)
Pulmonary embolism	1/98 (1%)		1/99 (1%)
Chronic obstructive pulmonary disease	1/98 (1%)		1/99 (1%)
Acute respiratory distress syndrome	1/98 (1%)		0/99 (0%)
Skin and subcutaneous tissue disorders
Skin reaction	1/98 (1%)		0/99 (0%)
Vascular disorders
Hypertension	1/98 (1%)		1/99 (1%)
Hypotension	1/98 (1%)		0/99 (0%)
Deep vein thrombosis	2/98 (2%)		0/99 (0%)
Other (Not Including Serious) Adverse Events
	AC --> ABI-007		AC --> Taxol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/98 (99%)		99/99 (100%)
Blood and lymphatic system disorders
Anaemia	50/98 (51%)		44/99 (44.4%)
Neutropenia	29/98 (29.6%)		24/99 (24.2%)
Leukopenia	13/98 (13.3%)		14/99 (14.1%)
Thrombocytopenia	8/98 (8.2%)		5/99 (5.1%)
Cardiac disorders
Palpitations	7/98 (7.1%)		2/99 (2%)
Ear and labyrinth disorders
Ear pain	5/98 (5.1%)		2/99 (2%)
Tinnitis	2/98 (2%)		5/99 (5.1%)
Eye disorders
Lacrimation increased	9/98 (9.2%)		10/99 (10.1%)
Vision blurred	9/98 (9.2%)		7/99 (7.1%)
Gastrointestinal disorders
Nausea	77/98 (78.6%)		79/99 (79.8%)
Constipation	47/98 (48%)		40/99 (40.4%)
Diarrhoea	35/98 (35.7%)		35/99 (35.4%)
Vomiting	38/98 (38.8%)		29/99 (29.3%)
Stomatitis	17/98 (17.3%)		27/99 (27.3%)
Abdominal pain	16/98 (16.3%)		9/99 (9.1%)
Abdominal pain upper	9/98 (9.2%)		4/99 (4%)
Dry mouth	2/98 (2%)		7/99 (7.1%)
Dyspepsia	19/98 (19.4%)		25/99 (25.3%)
Dysphagia	4/98 (4.1%)		6/99 (6.1%)
Gastrooesophageal reflux disease	12/98 (12.2%)		10/99 (10.1%)
Gingival bleeding	6/98 (6.1%)		3/99 (3%)
Glossodynia	5/98 (5.1%)		1/99 (1%)
Haemorrhoids	13/98 (13.3%)		10/99 (10.1%)
Oral pain	8/98 (8.2%)		5/99 (5.1%)
Rectal haemorrhage	8/98 (8.2%)		3/99 (3%)
General disorders
Fatigue	81/98 (82.7%)		77/99 (77.8%)
Mucosal inflammation	37/98 (37.8%)		30/99 (30.3%)
Pyrexia	21/98 (21.4%)		25/99 (25.3%)
Oedema peripheral	12/98 (12.2%)		14/99 (14.1%)
Chest pain	7/98 (7.1%)		8/99 (8.1%)
Asthenia	11/98 (11.2%)		6/99 (6.1%)
Catheter site pain	5/98 (5.1%)		1/99 (1%)
Chills	8/98 (8.2%)		4/99 (4%)
Pain	7/98 (7.1%)		7/99 (7.1%)
Tenderness	5/98 (5.1%)		1/99 (1%)
Immune system disorders
Seasonal allergy	3/98 (3.1%)		5/99 (5.1%)
Infections and infestations
Upper respiratory tract infection	24/98 (24.5%)		15/99 (15.2%)
Urinary tract infection	13/98 (13.3%)		16/99 (16.2%)
Fungal infection	6/98 (6.1%)		0/99 (0%)
Nasopharyngitis	5/98 (5.1%)		6/99 (6.1%)
Pharyngitis	5/98 (5.1%)		2/99 (2%)
Rhinitis	8/98 (8.2%)		4/99 (4%)
Sinusitis	11/98 (11.2%)		11/99 (11.1%)
Injury, poisoning and procedural complications
Bloody airway discharge	5/98 (5.1%)		4/99 (4%)
Contusion	5/98 (5.1%)		0/99 (0%)
Radiation skin injury	11/98 (11.2%)		6/99 (6.1%)
Investigations
Weight decreased	14/98 (14.3%)		14/99 (14.1%)
Metabolism and nutrition disorders
Anorexia	26/98 (26.5%)		20/99 (20.2%)
Dehydration	8/98 (8.2%)		10/99 (10.1%)
Decreased appetite	6/98 (6.1%)		9/99 (9.1%)
Hypokalaemia	6/98 (6.1%)		3/99 (3%)
Musculoskeletal and connective tissue disorders
Arthralgia	54/98 (55.1%)		48/99 (48.5%)
Myalgia	45/98 (45.9%)		41/99 (41.4%)
Pain in extremity	26/98 (26.5%)		27/99 (27.3%)
Bone pain	14/98 (14.3%)		14/99 (14.1%)
Back pain	11/98 (11.2%)		16/99 (16.2%)
Chest wall pain	6/98 (6.1%)		6/99 (6.1%)
Muscle spasms	5/98 (5.1%)		4/99 (4%)
Neck pain	3/98 (3.1%)		5/99 (5.1%)
Pain in jaw	5/98 (5.1%)		2/99 (2%)
Shoulder pain	5/98 (5.1%)		9/99 (9.1%)
Nervous system disorders
Headache	42/98 (42.9%)		41/99 (41.4%)
Neuropathy	39/98 (39.8%)		38/99 (38.4%)
Neuropathy peripheral	30/98 (30.6%)		24/99 (24.2%)
Dysgeusia	17/98 (17.3%)		22/99 (22.2%)
Peripheral sensory neuropathy	19/98 (19.4%)		18/99 (18.2%)
Dizziness	17/98 (17.3%)		16/99 (16.2%)
Paraesthesia	6/98 (6.1%)		9/99 (9.1%)
Amnesia	1/98 (1%)		5/99 (5.1%)
Hypoaesthesia	6/98 (6.1%)		5/99 (5.1%)
Migraine	1/98 (1%)		5/99 (5.1%)
Sinus headache	2/98 (2%)		5/99 (5.1%)
Psychiatric disorders
Insomnia	27/98 (27.6%)		26/99 (26.3%)
Anxiety	10/98 (10.2%)		15/99 (15.2%)
Depression	10/98 (10.2%)		13/99 (13.1%)
Renal and urinary disorders
Proteinuria	12/98 (12.2%)		11/99 (11.1%)
Dysuria	4/98 (4.1%)		8/99 (8.1%)
Reproductive system and breast disorders
Breast pain	3/98 (3.1%)		7/99 (7.1%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	45/98 (45.9%)		38/99 (38.4%)
Cough	27/98 (27.6%)		37/99 (37.4%)
Pharyngolaryngeal pain	23/98 (23.5%)		25/99 (25.3%)
Dyspnoea	16/98 (16.3%)		20/99 (20.2%)
Rhinorrhoea	15/98 (15.3%)		12/99 (12.1%)
Dysphonia	10/98 (10.2%)		9/99 (9.1%)
Nasal congestion	8/98 (8.2%)		5/99 (5.1%)
Postnasal drip	1/98 (1%)		5/99 (5.1%)
Respiratory tract congestion	5/98 (5.1%)		4/99 (4%)
Rhinitis allergic	0/98 (0%)		9/99 (9.1%)
Sinus congestion	3/98 (3.1%)		5/99 (5.1%)
Skin and subcutaneous tissue disorders
Alopecia	61/98 (62.2%)		66/99 (66.7%)
Rash	28/98 (28.6%)		22/99 (22.2%)
Nail disorder	28/98 (28.6%)		20/99 (20.2%)
Erythema	8/98 (8.2%)		12/99 (12.1%)
Dry skin	6/98 (6.1%)		11/99 (11.1%)
Skin hyperpigmentation	4/98 (4.1%)		13/99 (13.1%)
Pruritus	8/98 (8.2%)		8/99 (8.1%)
Blister	3/98 (3.1%)		5/99 (5.1%)
Nail discolouration	5/98 (5.1%)		2/99 (2%)
Night sweats	6/98 (6.1%)		2/99 (2%)
Palmar-Plantar erythrodysaesthesia syndrome	10/98 (10.2%)		7/99 (7.1%)
Skin exfoliation	4/98 (4.1%)		5/99 (5.1%)
Vascular disorders
Hot flush	33/98 (33.7%)		30/99 (30.3%)
Hypertension	27/98 (27.6%)		33/99 (33.3%)
Flushing	5/98 (5.1%)		2/99 (2%)
Lymphoedema	5/98 (5.1%)		7/99 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.