A Trial of 2 Schedules of Ixabepilone Plus Bevacizumab and Paclitaxel Plus Bevacizumab for Breast Cancer

Inclusion criteria:

* Locally recurrent or metastatic breast cancer, previously untreated with chemotherapy for advanced disease.
* At least 1 target lesion per RECIST criteria. Locally recurrent disease must not be amenable to resection with curative intent.
* No previous cytotoxic chemotherapy for locally recurrent/metastatic disease.
* Relapse 12 months or more after completing prior adjuvant or neoadjuvant taxane therapy.
* No previous breast cancer known to overexpress or amplify the human epidermal growth factor receptor 2 gene.
* Prior hormonal therapy in adjuvant, recurrent, or metastatic setting allowed but must have been discontinued at least 2 weeks before randomization.
* Karnofsky performance status of 80 to 100 or Eastern Cooperative Oncology Group performance status of 0 to 1.
* Estimated life expectancy of at least 12 weeks.
* Recovery from recent therapy (except for alopecia), including chemotherapy, immunotherapy, biologic therapy, or investigational product. Any such therapy must have been completed at least 3 weeks before randomization and at least 6 weeks from use of nitrosourea, or mitomycin.
* Recovery from recent surgery and radiation therapy. At least 1 week since minor surgery and/or focal/palliative radiation therapy; at least 3 weeks from radiation; at least 4 weeks from major surgery; and at least 8 weeks from liver resection, thoracotomy, or neurosurgery.
* Absolute neutrophil count ≥1500/mm\^3.
* Hemoglobin ≥9 g/dL.
* Platelets ≥100,000/mm\^3.
* Total bilirubin ≤1.5 times the upper limit of normal (ULN).
* Aspartate aminotransferase or alanine aminotransferase ≤2.5\*ULN.
* Normal partial thromboplastin time and either international normalized ratio or prothrombin time \<1.5\*ULN.
* Serum creatinine ≤1.5\*ULN or 24-hour creatinine clearance \>60 mL/min.
* Urine dipstick for proteinuria \<2+ (negative, trace, or +1). Participants with ≥2+ proteinuria at baseline were to undergo 24-hour urine collection and demonstrate ≤1g of protein in 24 hours to be eligible.

Exclusion criteria:

* Women of child-bearing potential (WOCBP) unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 6 months after treatment with bevacizumab.
* Women who were pregnant or breastfeeding.
* Women with a positive pregnancy test on enrollment or prior to study drug administration.
* Sexually active fertile men, whose partners were WOCBP, not using an adequate method of birth control.
* Evidence of baseline sensory or motor neuropathy.
* Serious infection or nonmalignant medical illnesses uncontrolled or the control of which could be jeopardized by this therapy.
* History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, serious gastric ulcer, or bone fracture within 6 months of study entry.
* History of hypertensive crisis or hypertensive encephalopathy.
* Significant vascular disease.
* Clinically significant cardiovascular disease.
* Baseline left ventricular ejection fraction by multiple-gated acquisition scan or echocardiogram for subjects with prior exposure to anthracyclines not within institutional normal limits.
* Symptomatic peripheral vascular disease.
* History of high dose chemotherapy with bone marrow transplant or peripheral blood stem cell transplant within the previous 2 years.
* Evidence of bleeding diathesis or coagulopathy.
* Prior treatment with an epothilone or any antiangiogenic agent.
* Concurrent nonhealing wound, ulcer, or fracture.
* Any current or history of brain and/or leptomeningeal metastases. Psychiatric disorders or other conditions rendering the participant incapable of complying with the requirements of the protocol.
* Any concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix.
* Known allergy to any of the study drugs or their excipients.